Walker-Wagner Syndrome 2095

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w: A symbol of map distance. ▶θ, ▶map distance,▶cM, ▶recombination, ▶mapping function

W Chromosome: This corresponds to the Y chromo-some in heterogametic females, WZ in birds andbutterflies. ▶chromosomal sex determination

w Locus: The first mutation discovered in Drosophilaby Morgan is involved in the control, production anddistribution of brown (ommochrome) and red (pteri-dine) pigments of the eyes and ocelli and some otheranatomical structures. The gene (at 1–1.5) apparentlyencodes an ATP-binding membrane transport proteinfor the precursors of the pigments. More than 200alleles have been identified within a 0.03 centiMorganregion, which has beenmapped by intragenic recombi-nation into 7 domains. The wild type allele isincompletely dominant over many mutant alleles.The alleles do not show partial complementation withthe exception of the wsp (white spotted) allele thatdisplays allelic complementation with the majority ofother alleles in the presence of the za (zeste). The latteris a regulatory gene at 1–1.0 location and zeste encodesa specific protein binding to the promoters of w,Ultrabithorax (Ubx) anddecapentaplegic (dpp).▶mapunit, ▶recombination, ▶morphogenesis in Drosophi-la, ▶eye color, ▶Tangier disease

WMutagenesis: A tendency of increased mutation afterWeigle reactivation. ▶Weigle; Yatagai F et al 1983Adv Space Res 3(8):65.

W Point: A stage just before the S phase when animalcells still have serum growth factor requirement toenter the S phase. ▶cell cycle

W Reactivation: This is the same as Weigle reactivation.

Waardenburg Syndrome: Autosomal dominant formsmay be distinguished on the basis of displacement(type I) and without displacement (type II) of theeyelids. Variegation in the color of the iris, whiteforelock, eyebrows and eyelashes, syndactyly, heartproblems, hearing defects may occur as autosomalrecessive anomaly. Dominant mutations in the SOX10gene may affect the neural crest-derived cell lineages.The Waardenburg syndrome type 2 gene (MITF[microphthalmia-associated transcription factor]) con-verts fibroblasts into melanocyte-like cells by transac-tivation of a tyrosinase gene. If MITF is inactivehypopigmentation occurs. Mutation in the PAX3transcription factor is responsible for hearing andpigmentationdefects of type 1 formcausedby failure of

transactivation of MITF. Human chromosomal loca-tions are type I 2q35, type IIA 3p14.1-p12.3 andtype IIB 1p21-p13.3. The type III form also calledKlein-Waardenburg syndrome is at 2q35 location.The syndrome may be haplo-insufficient. The merlephenotypes observed in several breeds of dogs arecharacterized by hypopigmentation and by hearing andeyedefects is causedby insertionofSINEelements intothe SILV (silver) gene, responsible for pigmentation.The merle phenotype is similar to the Waardenburgtype II anomaly (Clark LA et al 2006 Proc Natl AcadSci USA 103:1376). ▶PAX, ▶DiGeorge syndrome,▶eye defects, ▶eye color, ▶polydactily, ▶micro-phthalmos, ▶haplo-insufficient, ▶Shah-Waardenburgsyndrome, ▶dog; Sánchez-Martín M et al 2002 HumMol Genet 11:3231.

Waardenburg-Shah Syndrome: ▶Shah-Waardenburgsyndrome

WAF: ▶p21

WAGR: ▶Wilms tumor

Wahlund’s Principle: When two populations, each withdifferent allelic frequencies andboth inHardy-Weinbergequilibrium, are mixed by migration, there is an overalldecrease in heterozygotes: H ¼ 2p q½1� ðs2=p qÞ�:The decrease in overall heterozygosity indicates thedegree of heterogeneity between the two populationsand (σ2/p q ) is the Wahlund’s variance of genefrequencies. ▶allelic frequencies, ▶migration; YasudaN 1968 Am J Hum Genet 20:1.

Wald-Wolfowitz Test: Used for comparison of twounmatched, supposedly continuous distributions andthe null hypothesis is that the two samples aredistributed identically. ▶null hypothesis, ▶logisticregression; Hays WL, Winkler RL 1970 Statistics:Probabilitity, Inference, and Decision. Holt, Reinhartand Winston, New York.

Waldemar of Prussia: A hemophiliac great-grandson ofQueen Victoria.▶hemophilia A, ▶Queen Victoria

Waldenstrom Syndrome: ▶macroglobulinemia

Walker Boxes (P-loops): These are nucleotide triphos-phate-binding amino acid sequences in several pro-teins. Box A promotes branch migration in Hollidayjunctions during recombinationmediated by the RuvBprotein.Walker A: GlyXXGlyXGlyLysThr,Walker B:AspGluXAsp. The Lys residue binds the γ-phosphateof nucleotides directly.▶branch migration,▶Hollidayjunction, ▶RuvABC; Walker JE et al 1982 EMBO J1:945; Hishida T et al 2001 J Biol Chem 274:25335.

Walker-Wagner Syndrome: An autosomal recessivehydrocephalus (accumulation of fluid in the enlarged

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head) generally associated with retinal detachment,congenital muscular dystrophy and lissencephaly.▶Miller-Dieker syndrome, ▶hydrocephalus, ▶prena-tal diagnosis,▶head/face/brain defects,▶lissencephaly

Walker-Warburg Syndrome (HARD, 9q31): Refers toautosomal recessive hydrocephalus agyria and retinaldysplasia that was originally described as lissence-phaly. ▶Miller-Dieker syndrome; Beltrán-Valerode Barnabé D et al 2002 Am J Hum Genet 71:1033.

Walking: ▶chromosome walking

Walking of Transcriptase: Describes transient halting ofthe movement of the RNA polymerase ternarycomplex (polymerase, DNA, transcript) by sequen-tially providing subsets of the four ribonucleotides.▶transcript elongation

Wallaby: Wallabia bicolor, 2n = 11 in males and 10 infemales; Wallabia eugenii 2n = 16.

Wallaby: A non-viral retrotransposable elementnamed after the jumping small Australian kangaroo.▶retroposon

Walnut (Juglans spp): Occurs in both wild andcultivated forms; 2n = 2x = 32.

Walnut Comb: In poultry, it is determined by the geneticconstitution RrPp, and as a result of epistasis, occursin 9/16 frequencies in F2 after brother-sister matingof the same double heterozygotes (see Fig. W1).The other phenotypes in the segregating F2 are roseRr/RR, pp (3), pea rr, PP/Pp (3), and single pp, rr (1).

Walrus: Odobenus rosmarus, 2n = 32.

Waltzing Mouse: A chromosomal deletion causinginvoluntary movements.

Wanda: ▶fish orthologous genes

Wandering Spots: An older method of sequencing shortoligonucleotides. (Le Gall O et al 1988 J Gen Virol69:423).

Warburg Effect: ▶glycolysis

Warburg Micro Syndrome (2q21.3): A conditioncharacterized by autosomal recessive microcephaly,micropupil, congenital cataract, mental and physicalretardation, underdeveloped genitalia, facial

Figure W1. From left to right: Walnut, Rose, Pea, Single co

hairiness, hypoplasia of the corpus callosum andother anomalies. The molecular defect appears to bein the RAB3 GTPase activating protein. ▶corpuscallosum,▶RAB,▶Griscelli syndrome; Aligianis IAet al 20005 Nature Genet 37:221.

Ward-Romano Syndrome (WRS, 11p15.5): An autoso-mal dominant or recessive LQT disease involvinganomalousheartmuscle fibrillations, fainting (syncope)and possibly sudden death. It is the same as long QTsyndromes. ▶LQT, ▶electrocardiography, ▶ion chan-nels,▶HERG,▶Jarvell and Lange-Nielson syndrome,▶long QT syndrome,▶Andersen syndrome

Warfarin (C19H16O4, named after Wisconsin AlumniResearch Foundation): This is a slightly bitter, waterand alcohol soluble compound. It depresses the for-mation of prothrombin, necessary for blood clotting,andmay cause fragility of the capillary veins leading tohemorrhages. It is used in certain surgeries andtreatment of diseases that block arteries by blood clots.It is also a rodent poison. A single ingestion may notnecessarily be very hazardous to humans but rats ormice consuming it repeatedly in baits suffer internalbleeding and die. The antidote ofwarfarin is vitaminK.Warfarin inhibits vitamin K epoxide reductase. Muta-tions in rodents may make them resistant to warfarin.▶anticoagulation factors, ▶prothrombin deficiency,▶coumarin-like drug resistance, ▶vitamin K-dependent clotting factors, ▶chondrodysplasia; VanAken H et al 2001 Clin Appl Thromb Hemost 7:195;Loebstein R et al 2001Clin Pharmacol Ther 70(2):159.

Wasp: Wiskott-Aldrich syndrome proteins that regulatethe assembly of actin monomers into filaments andregulate the cytoskeletal organization and motility ofcells. WASF1 encoded at 6q21-q22 and WASF3 at13q13 are effectors for the signal transmission fromtyrosine kinase receptors to the cytoskeleton. Thefunction of WASF2 (1p36.11-p34.3) is also similar.The latter has a pseudogene at Xp11.22. ▶Wiskott-Aldrich syndrome, ▶actin, ▶cytoskeleton; Ward MEet al 2004 Proc Natl Acad Sci USA 101:970.

Wasp: Habrobracon spp. 2n = 20 for female, 2n = 10for male. The males hatch from unfertilized eggs andare haploid. The females come from fertilized eggsand are diploid. They are heterozygous for any of the

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nine sex factors. As a result of inbreeding, sex factorhomozygotes occasionally arise that are sterile “bipa-rental males” (see Fig.W2). Gynandromorphs occur inwasps but these are different from those inDrosophilabecause the haploid sectors are not necessarily malesectors as expected from the loss of one set ofchromosomes. Although in insects circulating sexhormones do not seem to exist, some type of diffusiblesubstance affects the chromosomally male sectors.Exceptional gynandromorphsmay arise by fertilizationof binucleate eggs. Gynandromorphic tendency isgenetically determined. ▶social insects, ▶honey bee;Page RE et al 2002 Genetics 160:375; Cowan DP,Stahlhut JK 2004 Proc Natl Acad Sci USA 101:10374.

Figure W2. Wasp (Right-side wings and legsremoved)

Watercress (Rorippa nasturtium-aquaticum): This is anorthern European vegetable with x = 16 but thespecies may be diploid, sterile triploid or tetraploid.

Watermelon (Citrullus vulgaris): An annual fruit, 2n = 22.Triploids are grown commercially and crossing tetra-ploid plants with diploids produces the seeds. The fruitsof the triploid plants are practically seedless and aretherefore easier to eat (see Fig.W3). According to somereports, triploids have a higher sugar content than eitherof the parental forms.

4n 3n 2n

Figure W3. Watermelon. (Diagram of watermelonsmodified after Eigsti OJ, Dustin P Jr 1955 Colchicine,Iowa State College Press, Ames, Iowa)

Watson and Crick Model: This has been describedby Watson JD, Crick FHC in 1953 (Nature [Lond]171:964) and it became the world’s most famousbiological model ever conceived. (See Fig. W4 of themodel, and Fig. W6 for historical documents: http://osulibrary.orst.edu/specialcollections/coll/pauling/dna/).It is interesting to note in the first DNA models of

Watson and Crick (1953) only two hydrogen bondshave been shownbetweenGandC.The third hydrogenbond between G and C was first mentioned in a paperby Pauling and Corey in 1956 (Waine-Hobson S 2006Nature [Lond] 439:539). The genome of the firsthuman being that was entirely sequenced in 2007belongs to James Watson (Project Jim). He agreed thathis DNA sequence should be added to public databasesbut requested that his ApoE gene status – which isindicativeof a risk forAlzheimer’s disease–beblankedout. It is likely that other disease susceptibility genesequences will not be made public either (Marshall E2007 Science 315:1780).

Watt (W): The product of volts and amperes in the caseof direct current. 1W= 1 joule/sec = 0.293 calories/sec=1/735HP (horsepower). Inotherwords, 1Wpower isgenerated by the electric potential between two pointsof 1 volt and 1 ampere current.▶volt, ▶ampere

Wax Coat: ▶eceriferum

WCPP (whole chromosome painting probe): Contains acombination of many probes, specific for a singlechromosome and thus may label with color its entirelength. The multicolor labeling probes may permitthe differentiation of all chromosomes in a singlekaryotype. ▶chromosome painting, ▶USP, ▶FISH,▶GISH

WD-40: Refers to a repeat (N) motif of tryptophan (W) -aspartic acid (D) in several eukaryotic regulatoryproteins (absent in prokaryotes) (see Figs. W5): WDrepeats are involved in signal transduction, RNAprocessing, developmental regulation, cell cycle,vesicular traffic, etc. ▶signal transduction; Neer EJet al 1994Nature [Lond]371:2987; SmithTF et al 1999Trends Biochem Sci 24:181.

W-DNA: Refers to a left-handed zig-zag duplex with thesame directions as B-DNA but other characteristicsmatch those of the Z-DNA. ▶DNA types

Weasel: Mustela erminea, 2n = 44; Mustela frenata,2n = 44.

WEB Service: This is a standard system of communica-tion of machines in a network.

WEBB (WB): A very rare blood group involving analtered glycosylation of glycophorin. ▶glycophorin,

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Figure W4. The double-stranded DNA molecule is joined through 2 and 3 hydrogen bonds between the A = Tand G≡C

nucleotides, respectively. The staircase-like ribbons represent the sugar-phosphate backbone of the double helix. During

replication the old plectonemic strands unwind and each old separated strand serves as a template for the formation of the

new molecules that are composed from one old and one new single strand (▶DNA replication,▶replication fork). This is,

therefore, known as the semi-conservative mode of replication. The model is consistent with most genetic phenomena

(mutation, recombination, gene expression, etc.). Since themodel was originally proposed, the details of the mechanisms

of the DNA transactions have been worked out in greater detail but basically none of the essential features had to be

revised. This model served as a basis for the central dogma of genetics indicating that the flow of information is from

the DNA to the RNA and to protein. During the 1960s it was discovered that through reverse transcriptase information can

be directed by reverse transcription from the RNA to the DNA but not from protein to the RNA and the DNA. The discovery

of prions makes the role of proteins in heredity somewhat ambiguous. All other proposals concerning hereditary

molecules (besides the DNA and the RNA) have now faded into oblivion

( (X6–94

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Figure W5. WD-40

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▶Gerbich, ▶En, ▶MN, ▶blood groups; Reid MEet al 1985 Biochem J 232:289.

WEBIN: A nucleotide sequence information form tothe EMBL database. It is offered by the European

Bioinformatics Institute: http://www.ebi.ac.uk/embl/Submission/webin.html; Webin qualifiers: http://www.ebi.ac.uk/embl/WebFeat/index.html.

WEE1: A protein kinase which inactivates the CDK1/cdc2 gene product through phosphorylation of thetyrosine-15 residue. Wee1 is subject to proteolysisin a Cdc34-dependent way before the S phase canbe completed. ▶kinase, ▶Mik1, ▶cell cycle, ▶cdc,▶checkpoint; Tzivion G et al 2001 Oncogene20:6331; Bartholomew CR et al 2001 Mol Cell Biol21:4949; crystal structure: Squire CJ et al 2005Structure 13:541.

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Figure W6. The Watson & Crick model as represented by Josse JJ, Kaiser AD, and Kornberg A, 1961 J Biol Chem

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Wegener Granulomatosis: An autosomal dominant con-dition characterized by the presence of a ~29 kDaserine protease antigen, identical to myeloblastin.It is a very serious ailment primarily affecting theupper and lower airways and kidneys. ▶myeloblast,▶Goodpasture syndrome

Weibel-Palade Bodies: These are 0.1–0.2 μm × 4 µmmembrane-enclosed bodies found around the plate-lets or in the endothelium of all animals. They storein their 150–200 Å tubules the von Willebrandglycoprotein. ▶von Willebrand disease; Denis CVet al 2002 Proc Natl Acad Sci USA 98:4072.

Weighted Mean: Refers to the calculated mean multi-plied by the pertinent frequency, e.g., in a populationthe mean value of the homo- and heterozygousdominants (AA and Aa) is 250 and that of the

homozygous recessives (aa) is 200, and the respectivefrequencies are 0.8 and 0.2, then theweightedmean ofthe population is (250 × 0.8) + (200 × 0.2) = 240.▶mean

Weigle Mutagenesis: Denotes an increase in mutationof phage by mutagenic treatment of the host. (SeeWeigle JJ 1953 Proc Natl Acad Sci USA 39:628;Bhattacharyya SC et al 1991Can JMicrobiol 37:265).

Weigle Reactivation: An increase in phage survivalwhen mixed with host cells exposed to low doses ofUV light. ▶DNA repair, ▶marker rescue, ▶multi-plicity reactivation; Calsou P, Salles B 1991 Mol GenGenet 226:113.

Weismannism: Inheritance takes place by the transmis-sion of the genetic determinants through the germ line(Keimbahn) and environmentally-induced phenotypic

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variations are not inherited. ▶germ line; Weismann A1985 Die Continuität des Keimplasmas als Grundlageeiner Theorie der Vererbung. Fischer, Jena, Germany.

Weissenbacher-Zweymuller Syndrome (WZS, 6p21.3):A condition characterized by neonatal small jaws(micrognathia), hip and/or shoulder bone defects(rhizomelic chondrodysplasia), general underdevel-opment of bones that may improve in later years opticnerve defects, myopia and deafness. Some of thesymptoms resemble those of the Stickler syndrome.The basic defect is in the collagen gene COL11A2.▶collagen, ▶Stickler syndrome

Welander Distal Myopathy (WDM, 2p13): A dominantlate-onset muscular dystrophy.▶muscular dystrophy,▶Miyoshi myopathy

Werdnig-Hoffmann Disease: A recessive (5q12.2-q13)infantile muscular dystrophy primarily affecting thespinal cord muscles. The prevalence is approximately1 × 10–4. The gene frequency has been estimated to bearound 0.014 and the frequency of heterozygotes about0.02. It encodes a protein that shows homology todystrophin. The survival rate varies according to theseverity of symptoms. A subunit of transcription factorTFIIH usually suffers deletions. ▶dystrophin, ▶mus-cular dystrophy, ▶neuromuscular diseases, ▶spinalmuscular atrophy,▶transcription factors

Werner Syndrome (WRN): Involves premature aging,hardening of the skin, cataracts, atherosclerosis,diabetes mellitus, etc. The gene expression profile issimilar to that seen in normal aging (Kyng KJ et al2003 Proc Natl Acad Sci USA 100:12259). Culturedcells have higher chromosome breakage and mutabil-ity. Neoplasias develop frequently. Ulceration aroundthe ankles and soft tissue calcification are symptomsof this condition, unrelated to aging. It was earlier heldthat the recessive defect was controlled by humanchromosome Xp12-p11.2 but recent linkage informa-tion, including complete sequencing on the basis ofpositional cloning, confirms its location at 8p12.WRN contains four structurally folded domainscomprising an exonuclease, a helicase, a winged-helix and a helicase-and-ribonuclease D/C-terminaldomain. The protein is required for focus formingactivity in DNA replication (FFA). It contains 1,432amino acids and resemblesRecQ typeATP-dependenthelicases (homologous to budding yeast SGS1 andSRS2 genes). Defects in the helicase (frameshift,nonsense mutation) explain most of the symptomsin terms of a flaw in DNA metabolism. WRN alsointeracts with DNA polymerase δ. However, theamino end domain ofWRN shows 3′→5′ exonucleaseactivity and it may be involved in genetic recombi-nation and/or repair. Forced telomerase activitysubstantially extends the life span of cultured WRN

cells. The WRN gene may be inactivated by CPGisland hypermethylation at its promoter. Since WRNinvolves DNA repair, inactivation may lead to lossof exonuclease-mediated DNA repair and increasedchromosomal instability as well as to apoptosis,induced by a camptothecin analog (irinothecan), atopoisomerase inhibitor. Thus, cancer cells maybecome more amenable to chemotherapy (Agrelo Ret al 2006 Proc Natl Acad Sci USA 103:8822). Normalfibroblasts and U20S osteosarcoma cells rendereddeficient in WRN exhibit reduced phosphorylation ofp53 and histoneH2AX in response toT-oligo (telomeresingle-strand overhang) treatment indicating its role inthe processing of telomeric DNA and subsequentactivation of DNA damage responses (Eller MS et al2006 Proc Natl Acad Sci USA 103:15073). There isevidence that the genome instability in WS cellsdepends directly on telomere dysfunction, linkingchromosome endmaintenance to chromosomal aberra-tions in this disease (Crabbe L et al 2007 ProcNatl Acad Sci USA 104:2205). ▶aging, ▶progeria,▶helicase,▶exonuclease,▶FFA,▶Bloom syndrome,▶co-suppression, ▶RNAi, ▶atherosclerosis, ▶telo-meres,▶translesion; Kamath-Loeb AS et al 2000 ProcNatl Acad Sci USA 97:4603; Shen J-C, Loeb LA 2000Trends Genet 16:213; Kawabe Y et al 2001 J BiolChem 276:20364; Kipling D et al 2004 Science305:1426.

Wernicke-Korsakoff Syndrome: A chromosome 3p14.3recessive disorder involving transketolase deficiencycaused by the lowered ability of the enzyme to bindthiamin pyrophosphate. Another transketolase defi-ciency has been traced to Xq28. This dysfunction ofenergy metabolism leads to neuropsychiatric anoma-lies, especially in alcoholics and when the level ofthiamin is low in the diet. ▶thiamine pyrophosphate

West Nile Virus (WNV, Flaviviridae): A single-strandedRNA virus. E-glycoprotein is its most importantprotein, both structurally and for infection (seeFig. W7). Of the two strains, lineage 1 has causedmost of the health problems in the US. Outbreaks ofthe epidemic have been described in Africa, the MidEast and southern Europe. About 29 species ofmosquitos transmit the virus to birds and from birdsto humans. In North America the human- and bird-biter forms of the Culex mosquitos form hybrids andmay facilitate the severity of transfer between thesespecies (Fonseca DM et al 2004 Science 303:1535).If infected mosquitos feed in close vicinity of non-infected individuals, the secreted saliva is sufficient fortransmission of the virus in an appreciable frequency(5.8%) even when the blood of vertebrates does notcontain the virus (non-viremic). This contributes tothe rapid spread of the disease (Higgs S et al 2005 ProcNatl Acad Sci USA 102:8871). The symptoms include

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fever, headache, gastrointestinal and mental changes(memory loss, depression); rash, cough and othersymptoms may also be manifested. The virus appearsgenetically quite stable. The fatality ranges from 4 to14% but in older or immune-compromised personsthe risks may be more than double. The most effectivediagnosis reveals immunoglobulin M (IgM) in the cer-ebrospinal fluids. RNAi holds promise for effectivemedication against viral encephalitis at least in mice.However, mosquito control is the key to prevention.

FigureW7. WestNile viruswithheavycapsuleand twoconcentric lipid layers surrounding the core with RNA

DNA vaccine coding for the RNA transcript ofthe related Kunjin flavovirus has protective effectsagainst the West Nile Virus (Hall RA 2003 Proc NatlAcad Sci USA 100:10460). ▶immunization genetic,▶viral encephalitis; Petersen LR, Marfin AA 2002Annals Int Med 137:E173; Brinton MA 2002 AnnuRevMicrobiol 56:371; http://westnilemaps.usgs.gov;http://www.cdc.gov/ncidod/dvbid/westnile/.

West Syndrome (ARX, Xp22.13; ISSX, Xp21.3-p22.1):This involves an X-linked central nervous defect,hypsarrhythmia (electroencephalographic anomaly)resulting in infantile spasms and mental retardation.Its incidence is 2–5 × 10−4 at birth. The basic defectmay be in the serine-threonine kinase 9 region.▶epilepsy, ▶mental retardation X-linked; KalscheuerVM et al 2003 Am J Hum Genet 72:1401.

Western Blot (Western hybridization): Refers to theidentification of polypeptides separated electropho-retically on SDS polyacrylamide gels, then trans-ferred to nitrocellulose filter and labeled byimmunoprobes such as radioactive or biotinylatedantibodies. ▶immunoblotting, ▶gel electrophoresis,▶far-western hybridization; Towbin H et al 1979Proc Natl Acad Sci USA 76:4350; BurnetteWN 1981Anal Biochem 112:95.

Weyers Acrofacial/Acrodental Dysostosis: An allelicvariation in the gene locus at 4p16 encoding theEllis-van Creveld syndrome. ▶Ellis-van Creveldsyndrome

WGRH (whole genome radiation hybrid): Formed whenthe donor is a diploid cell line for the generation ofradiation hybrids. ▶radiation hybrid; Vignaux F et al1999 Mamm Genome 10:888.

WGA (whole genome association, whole genome assem-bly, whole genome array). Whole genome associa-tion study attempts to identify all the genetic factorsinvolved in the development of a particular disease.The PLINK software tool can handle a very largeset of data involving five main domains of function:data management, summary statistics, populationstratification, association analysis, and identity-by-descent estimation (Purcell S et al 2007 Am J HumGenet 81:559). ▶microarray hybridization, ▶genomeannotation

WGS (whole-genome shotgun sequencing): Developedby Craig Venter and associates at Celera Genomics,Rockville, MD, USA. The genome is sheared into afew thousand base pair long pieces and cloned intosequencing vectors. Each fragment end (~500 bp)is covered by the sequencing several times andthen assembled into overlapping segments by end-sequences. In thisway oriented, contiguous sequences(contigs or scaffolds) are generated. Between thescaffolds a physical gapmay remain until the physicalmap is “finished” and the complete genome isreconstructed with the aid of high-power computers.The scaffolds are also mapped to eukaryotic chromo-somes and chromosome arms with the aid ofsequence-tagged sites. The heterochromatic regions(mainly around the centromeres and near thetelomeres) are unstable when cloned and thus resistsequencing. These regions contain transposons andredundant ribosomal RNA genes with a few inter-spersed ORFs. For the repeated sequences the WGSmethod provides less resolution (She X et al 2004Nature [Lond] 431:927). The function of thesequences is indicated by annotation using Genscanor Genie computer software. ▶shotgun sequencing,▶mate pair, ▶sequence-tagged sites, ▶transposon,▶ribosomal RNA, ▶ORF, ▶annotation, ▶geneontology, ▶scaffolds in genome sequencing, ▶ge-nome projects; Adams MD et al 2000 Science287:2185; http://www.ncbi.nlm.nih.gov/projects/WGS/WGSprojectlist.cgi.

Whale: Baleonoptera species are 2n = 44; Kogiabreviceps, 2n = 42.

Wheat: ▶Triticum

Wheat Germ In Vitro Translation: Cell-free wheatgerm extracts can be used for the translation of viral,prokaryotic and eukaryotic mRNAs into protein. Thesupernatant of the extract must be chromatographi-cally purified from inhibitory endogenous amino

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acids and pigments before translation. Tritin, one ofthe endosperm proteins, inactivates the ribosomesand thus reduces the efficiency of the system unlesscarefully removed. The extract contains tRNA, rRNAand other factors required for protein synthesis.Phosphocreatin and phosphocreatine kinase additionsare needed for supplying energy. Spermidine is addedto stimulate the translation efficiency and preventpremature termination of the polypeptide chain.Magnesium acetate and potassium acetate, mRNA(to be translated) and amino acids (including one in aradioactively labeled form) are also necessary. Incuba-tion is at 25°C for 1 to 2 hours. In general, the procedureis very similar to the rabbit reticulocyte system.▶rabbitreticulocyte in vitro translation system; Erickson AH,Blobel G 1983 Methods Enzymol 96:38.

Whim Syndrome (2q21): Refers to hypogamma-globulinemia, neutropenia, myelokathexis (retentionof bone marrow neutrophils) and papilloma virussusceptibility due to mutations in the chemokinereceptor CXCR4. ▶gammaglobulin, ▶neutropenia,▶neutrophil,▶CXCR,▶papilloma virus; HernandezPA et al 2003 Nature Genet 34:70.

Whipple’s Disease: An infectious disease caused byTropheryma whipplei bacteria.

White Blood Cell: ▶leukocyte

White Forelock: ▶forelock, ▶white

White Leghorn (chicken): Has genes controlling thecolor of the plumage CC, OO, II; the color iswhite (see Fig. W8). C and O both are needed forpigmentation but I is an inhibitor of color. ▶WhiteSilkie, ▶White Wyandotte

Figure W8. White leghorn rooster

White Matter: ▶gray matter

White Silkie (chickens): They are of the constitution cc,OO, ii and have white feathers because only one ofthe two dominant genes,O, required for pigmentationis present. ▶White Leghorn, ▶White Wyandotte

White Wyandotte (chickens): They have the genes CC,oo, ii and are white because only one, C, of thetwo dominant genes is present but not the other, O.▶White Leghorn, ▶White Silkie

Whooping Cough: A respiratorydisease inhumans causedby the pertussis toxin of the bacterium Bordatellapertussis (3,816 genes). Species such as B. parapertus-sis (4,404 genes) and B. bronchiseptica (~5,007 genes)are related pathogenic species for various mammals(Parkhill J et al 2003 Nature Genet 35:32). ▶pertussistoxin,▶microfluidics

Whorl: Refers to a circular or spiral arrangement ofstructures, such as various parts of flowers or thedermal ridges in a human fingerprint. ▶fingerprint-ing, ▶flower differentiation

Wide Cross: Refers to hybridization between plants ofdifferent species or genera.

Widow’s Peak: An autosomal dominant pointed hairlinein humans (see Fig. W9).

Figure W9. Widow’s peak

Wilcoxon’s Signed-Rank Test: A non-parametric substi-tute for the t-test for paired samples (see Table W1).The desirable minimal number of paired samples is10 and it is expected that the population wouldhave a median, be continuous and symmetrical. Thedifferences between the variates are tabulated andranked; the largest receives the highest rank. In thecase of ties, each should be assigned to a shared rank.The smaller group of signed-rank values is thensummed as the T value. This T value is comparedwith figures in a statistical table. If the value obtainedis smaller than that in the body of the table underprobability and on the line corresponding to thenumber of pairs tested, then the null hypothesis isrejected and the conclusion is justified that the twosamples are different.

Example: Since T being 8.0 according to the firstline of Table T1, the difference between the twosets of data is significant at the level of 0.05probability but not at the 0.01 level.

Table W1. Wilcoxon’s Signed-Rank Test

Pairs Difference Signed Ranks Probability

+ − n 0.05 0.01

1 +6 7 10 10 5

2 +5 6 11 13 7

3 +10 10 12 17 10

4 �3 4 14 25 16

5 +4 5 16 35 23

6 +7 8 18 47 33

7 �2 3 20 60 43

8 �1 0.5 22 75 55

9 +9 9 24 91 69

10 �1 0.5 26 110 84

T = 8.0

Williams Syndrome 2103

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A more general procedure for determining theprobabilities depends on determining the Z value eitherfor threshold probabilities or more precisely by using atable of the cumulative normal variates (such as theBiometrika Tables for Statisticians, Vol. 1, Pearson ES,Hartley HO, (Eds.), Cambridge University Press,Cambridge). Z values larger than 1.960, 2.326 and3.291 correspond to P 0.05, 0.01 and 0.001, respective-ly. These probabilities rule out the null hypothesis.

Z¼m�T�0:5

sand m¼ nðnþ1Þ

4ands¼

ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

½2nþ1�m6

r

where n = the number of paired data.▶non-parametricstatistics, ▶Mann-Whitney test, ▶Student’s t distribu-tion, ▶QTL

Wild Type: The standard genotype (that is most commonin wild [feral] populations). ▶isoalleles

Wildervanck Syndrome: This appears to be a X-linkeddominant deafness, frequently associated with otherdisorders. Approximately 1% of deaf females isaffected by it. It does not occur in males, presumablybecause it is lethal when homo- or hemizygous. It hasbeen suggested that it is polygenically determined butthe mechanism of male exclusion is as yet unknown.▶deafness, ▶sex-limited, ▶imprinting

Wildfire Disease of Plants: Caused by the toxin(methionine analog) of the bacterium Pseudomonastabaci, and it leads to necrotic spots on the leaves.▶Pseudomonas

Williams Factor (Flaujeac factor deficiency): An auto-somal recessive mutation in human chromosome

3q26-qter causing deficiency of a high molecularweight kininogen, a precursor of a blood clotting factor.▶kininogen, ▶blood clotting pathways, ▶antihemo-philic factors

Williams Syndrome (Williams-Beuren syndrome,WMS): This autosomal dominant condition involvesstenosis (narrowing) of the aorta, arteries and lungs,elfin face (elfins are diminutive mythological crea-tures), malformation of teeth and stature, mentaldeficiency and excessive amounts of calcium in theblood (hypercalcemia) and in some tissues. Cognitiveabilities are impaired in an unusual fashion. Duringinfancy patients are poor in language skills but theirperformance is relatively better in numerical intelli-gence tests. By adulthood the trend is reversedindicating that these abilities are under the control oftwo different developmental modules. Various typesof deletions in different chromosomes (15, 4, 6) havebeen suspected. Chromosome-specific probes haverevealed a ~1.5 Mb deletion of 7q11.23. This regionharbors several genes including the GTF21RD1 basictranscription factor and the Williams syndrome tran-scription factor (WSTF/WCRF/ACF), which bearsstructural similarity to a 180 kDa chromatin-remodeling factor. The differences in the phenotypesof affected individuals may be due to the dosageeffect of the chromosomal segments of this tract.Lower calcium in the diet may alleviate some of thesymptoms. Vitamin D2 anomaly is suspected. Thefunction of the Williams factor is unrelated. Recentfindings have indicated the involvement of LIMKprotein kinases (carrying two LIM domains) thatare serine/threonine/tyrosine kinases and regulate

2104 Wilms Tumor

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actin in the cytoskeleton. Under normal conditionsRAC-GTP activates the LIM kinases that in turnphosphorylate cofilin and inactivate it. Dephosphor-ylation permits the formation of active cofilin that isassociated with actin. The actin—cofilin association isapparently mediated by phosphoinositides (PtdInsP2).Defects (heterozygosity for a mutation) in LIMK leadto abnormal neuronal connections. Elastin defectscharacterize the symptoms of the Williams syndrome.▶supravalvular aortic stenosis, ▶cutis laxa,▶cardiovascular diseases, ▶dwarfism, ▶vitamin D,▶Williams factor,▶LIM domain,▶face/heart defects,▶cofilin, ▶actin, ▶phosphoinositides, ▶human intel-ligence, ▶module, ▶Marfan syndrome, ▶BTK;Peoples R et al 2000 Am J Hum Genet 66:47;MorrisCA, Mervis CB 2000 Annu Rev GenomicsHum Genet 1:461; Sumi T et al 2001 J Biol Chem276:23092; Urbán Zs et al 2002 Am J Hum Genet71:30; Bayés M et al 2003 Am J Hum Genet 73:131;Tassabehji M et al 2005 Science 310:1184.

Wilms Tumor (WT): This is usually associated with adeletion in the short arm of human chromosome11 extending from 11p13 to 11p15.5 (WT1) spanningseveral genes and is frequently referred to as theWAGRsyndrome (Wilms tumor-aniridia-genitourinaryanomalies and RAS oncogene-like function). Thecondition is characterized by symptoms of all or partsof the functions implied by WAGR. Wilms tumor iscaused by a mutation in a cancer-suppressor transcrip-tion factor and splicing factorwith 4Zn finger domains.Wilms tumor is extremely complex and additionalWTgenes in chromosomes 16q, and 1p, 4p, 8p, 14p, 17pand q, 18q have also been implicated. The transcriptdisplays alternative splicing. Wilms tumor suppressorgene is expressed only in the maternally transmittedallele. Prevalence is about 10−4 during the first fiveyears of age. Recent evidence has revealed a WT genein the 17q12-q21 region. TheWT1 gene also regulatesmuscle differentiation. The WT1 gene affects the SRYlocus in the Y chromosome and that explains thesymptoms associated with genitourinary developmentwhen it is altered. The different functions are based onisoforms of the protein. ▶aniridia, ▶RAS, ▶deletion,▶hypertension, ▶kidney diseases, ▶Zinc finger,▶breast cancer,▶imprinting,▶isoform,▶Rhabdosar-coma, ▶Denys-Drash syndrome, ▶Frasier syndrome,▶acatalasemia; Hossain A, Saunders GF 2001 J BiolChem 276:16817; Hammes A et al 2001 Cell 106:319.

Wilson Disease (WD): Recessive disease encoded inhuman chromosome 13q14.2-q14.3. It affects pri-marily persons of age 30 and above although juvenileforms have also been described. The major symptomsare cirrhosis of the liver and psychological ailmentscaused by a deficiency of ceruloplasmin resulting incopper accumulation. In this as well as other diseases

involving cirrhosis of the liver, at the upper and lowermargin of the cornea (see Fig. W10) a greenishnarrow ring (↑) occurs. The basic defect is in a coppertransportingATPase of themitochondria. Inactivationof the enzyme (ATP7B or ATP7A) causes neurogen-eration and overexpression can lead to resistance totherapeutic drugs. Mutations in the N domain of theenzyme prevent tight ATP binding and can lead to>30 forms of Wilson disease (Dmitriev O et al 2006Proc Natl Acad Sci USA 103:5302).

Figure W10. Wilson disease

XIAP (X-linked inhibitor of apoptosis) inhibitscaspases and copper metabolism in WD and othercopper toxicosis diseases. Intracellular copper alters theconformation of XIAP and lowers its ability to inhibitcaspase. This results in sensitivity to apoptosis (MuftiARet al 2006MolCell 21:775). The prevalence ofWDin the USA is about 3 × 10−5. A similar anomaly hasbeen observed in Long-Evans Cinnamon (LEC) ratsthat may serve as an animal model for the study of thedisease. Prenatal diagnosis of offspring of carrierparents may be possible by using linkage with DNAmarkers.▶Menkes disease,▶acrodermatitis,▶hemo-chromatosis, ▶mitochondrial disease in humans,▶neurodegenerative diseases

Winged Helix Protein: This class of the helix-turn-helixproteins uses a β-hairpin (a wing) to bind the DNA.▶DNA-binding protein domains; Gajiwala KS,Burley SK 2000 Curr Opin Struct Biol 10:110.

Wingless (wg/Dint-1; 2–30):Drosophila gene is involvedinmorphogenetic signaling and its homologs are foundin all vertebrates and invertebrates. The mousehomolog is Wnt. Components of the Wnt cascade arealtered in breast and colon cancers in mice and inhumanmelanomas.ThepathofWg function is depicted(see Fig. W11).Fz ( frizzled trichomes) and Dally (division ab-

normally delayed, controls heparan sulfate) are

Glycogen synthase kinase

Receptor Fz

Receptor dally

Armadillo

Armadillo

Wg-responding genes are on

TCF and other proteins transcribed

Cell membrane Nuclear membrane

CKl→Dsh→Zw3

Figure W11. Path of Wg function

WL 2105

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G protein-like receptors. Dsh (dishevelled) mitigatesthe block by Zw3 (zeste white), Armadillo is a β-catenin-like protein. TCF (ternary complex factors)co-activate transcription. Dsh protein blocks glycogensynthase kinase (GSK3) that would be a negativeregulator of Armadillo. CK1 (a serine kinase, calledcasein kinase) phosphorylates Dsh~Zw. Actually, Wgis involved in more complex functions. Wg alsosignals to the epidermal growth factor (EGF) receptor.WNT-4 duplication in humans and mice masculinizesXX individuals. In the Sertoli andLeydig cells DAX1,an antagonist of SRY, is upregulated. The Wntpathway is involved in signaling to somatic stemcells and the maintenance of cancer (Reya T, CleversH 2005 Nature [Lond] 434:843). One study hasrevealed 238 potential regulators of the Wnt pathwayand half of them have human orthologs and several ofthem are involved in human disease (DasGupta R et al2005 Science 308:826). The secretion of Wnt ligandrequires a transmembrane protein (Wentless [Wls]/Eveness interrupted [Evi]). Wls is in chromosome 3of Drosophila within 68A/B band; homologs arepresent in the Caenorhabditis and human genomes(Bänziger C et al 2006 Cell 125:509; Bartscherer Ket al 2006 Cell 125:523). ▶organizer, ▶EGF, ▶Arma-dillo, ▶adrenal hypoplasia congenital, ▶sex reversal,▶catenins, ▶GSK, ▶TCF, ▶heparin sulfate, ▶mor-phogenesis in Drosophila, ▶zeste, ▶SRY, ▶Wolffianduct, ▶Gardner syndrome; Kühl M et al 2000 TrendsGenet 16:279; Peifer M, Polakis P 2000 Science287:1606; Wilkie GS, Davis I 2001 Cell 105:209;van de Wetering M et al 2002 Cell 109:S13; Peifer M,McEwen DG 2002 Cell 109:271; Mosimann C et al2006 Cell 125:327; review: Clevers H 2006 Cell 127:469; http://www.stanford.edu/~rnusse/wntwindow.html.

Winner’s Curse: A finance/business concept. In com-petitive bidding, the winner may be the loser. Thismay be the case when the highest bidder overestimatesthe value of an item/stock or any other object in abidding competition (e.g., at an auction) and it turns outthat, even if some preferential values are added, thevalue of the purchase is lower than estimated/expected.

A similar situation may be observed in populationgenetics when screening is conducted for a lowexpression, rare allele. Before the tests are carried outthe frequencyof carriers or homozygotes for thediseasecanbeonlyguessed. If the sizeof thepopulation studiedis too small, the information gathered may not bereliable and useful. If a very largepopulation is tested—at great expense—and the results are still ambiguous,the investment in labor and other means is notworthwhile. Thus, the winner (the thorough investiga-tor) suffers the curse of being a loser. ▶game theory,▶critical population size,▶mutation rate; examples forwinner’s curse: http://www.techcentralstation.com.

Wiskott-Aldrich Syndrome (WAS, Xp11.23-p11.22):ThisX chromosomal immunodeficiency disease causeseczema, reduced platelet size, bloody diarrhea, greatersusceptibility to infections, lymphocyte malignanciesandusually death before the age of 10.Theprevalence isabout 4 × 10−6. The affected individuals are deficientin a 115 kDa lymphocyte membrane protein and theplatelets are abnormally low in a glycoprotein(sialophorin). Carriers may be identified by linkage,lymphocyte analysis and nonrandom inactivation ofthe X chromosomes. WAS is allelic to the humanXp11.23 thrombocytopenia gene. This gene includes12 exons in 9 kb genomic DNA and encodes 502amino acids. The involvement of CDC42 signalingdefect is likely. Cdc42-GTP is a far better agonist forthe protein WASP than Cdc4 2-GDP (Leung DW,Rosen MK 2005 Proc Natl Acad Sci USA 102:5685).The WAS protein (WASP) mediates cytoskeletalrearrangement and transcriptional activation of Tcells. ▶immunodeficiency, ▶T cell, ▶cytoskeleton,▶thrombocytopenia, ▶thrombopathic purpura,▶cancer,▶CDC42,▶agonist,▶podosome,▶WASP,▶platelet; Silvin C et al 2001 J Biol Chem 276:21450;Devriendt K et al 2001 Nature Genet 27:313; Caron E2002 Current Opin Cell Biol 14:82.

Witkop Syndrome: ▶tooth-and-nail dysplasia

WL (working level): Used for the characterization ofshort-lived radon decay products in 1 liter of

2106 WNT1

W

air resulting in the ultimate emission of 1.3 × 10−5

MeV of alpha radiation energy. WL is also definedas 2.08 × 10−5 joule h m�3. WLM (working level/month) = exposure of 170 h at 1 WL. ▶radon

WNT1 (cysteine-rich glucoprotein ligand): The ~18vertebrate genes have numerous and diverse rolesin signaling to development, particularly along theanterior-posterior body axis. ▶INT1 oncogene inmouse, ▶wingless gene product in Drosophila,▶morphogenesis inDrosophila {63},▶pattern forma-tion, ▶organizer, ▶Gardner syndrome, ▶gonads;Skromme E, Stern CD 2001 Development 128:2915.

Wobble: The 5′-base of the anticodon can recognizemore than one kind of base at the 3′ position of thecodon, e.g., both U or C in the mRNA may pair withG, and both G and A may pair with U, or A or U, or Cmay recognize I (inosinic acid at the 5′-position in theanticodon). There is no AAA anticodon for Phe butthe GAA anticodon recognizes both UUU and UUCcodons in the mRNA. The GUU and GUC codons ofVal are decoded by an anticodon AAC. Inosinic acidoccurs in the anticodon of 8 tRNAs of highereukaryotes, in 7 of yeast and in the tRNAArg

2 ofprokaryotes and plant chloroplasts. Inosine may beformed from adenosine by adenosine deaminases.In tRNAs, however, a different dimeric deaminase,encoded in yeast by Tad2 and Tad3 genes, is active.This deaminase is related to the cytidine deaminase(CDA). According to the classical or universal geneticcode of 61 sense and 3missense codons, aminimum of32 tRNAswould be required to recognize all the aminoacids. Further simplifications permit protein synthesis,however, by 22–24 tRNAs. In the human genometRNA genes have been found all over the genomeyet 140 tRNA genes are crowded in a 4 Mb regionof chromosome 6. The altered mitochondrial coderequires modifications in the anticodon wobble.▶genetic code, ▶tRNA, ▶anticodon, ▶isoacceptortRNA, ▶mtDNA, ▶hypoxanthine, ▶decoding; CrickFHC 1966 J Mol Biol 19:548; Agris PF 1991Biochemie 73:1345; Lim VI 1994 J Mol Biol 240:8;Sibler AP et al 1986 FEBS Lett 194:131.

Wolbachia: Refers to an endocellularly infectious groupof bacteria of arthropods, nematodes and crustaceansthat are transmitted maternally and may cause femin-ization, cytoplasmic incompatibility and thelytoky.Wolbachia is localized to the stem cell niche ofDrosophila germarium (Frydman HM et al 2006Nature [Lond] 441:509). Infected males cannot pro-duce viable offspringwith uninfected females becauseof cytoplasmic incompatibility. They are compatible,however, with infected females and produceoffspring. In some Culex mosquitos variations havebeen found in cytoplasmic incompatibility controlled

by two prophage genes of Wolbachia involvingankyrin repeats (Sinkins SP et al 2005 Nature [Lond]436:257). Antibiotics can cure incompatibility inmanyinstances. The removal of Wolbachia by antibioticsfrom parasitic wasps stops oogenesis. Wolbachias asendosymbionts of filarial nematodes are responsiblefor the river blindness disease (filariasis). Wolbachiainfection of flies with some oogenesis defect causingDrosophila Sex-lethal alleles surprisingly restoresfertility (Starr DJ, Cline TW 2002 Nature [Lond]418:76).Wolbachiamay serve as an agent to block thespread of malaria by causing sterility in the insect host(Ito J et al 2002 Nature [Lond] 417:452). There areseveral related species. The W. pipientis genome of1,267,782 bp has been sequenced and it appears tocontain an unusually high number of mobile elementsas well as essential difference in metabolism comparedto related species e.g., Ricketsia (Wu M et al 2004PloS Biol 2:327). ▶cytoplasmic incompatibility,▶thelytoky, ▶symbionts hereditary, ▶segregationdistorter, ▶pronucleus, ▶Ricketsia, ▶ankyrin;Stouthammer R et al 1999 Annu Rev Microbiol53:71; Zimmer C 2001 Science 292:1093; Dedeine Fet al 2001 Proc Natl Acad Sci USA 98:6247; SaintAndré v A et al 2002 Science 295:1892; http://troi.cc.rochester.edu/~wolb/FIBR/database.html.

Wolcott-Rallison Syndrome (WRS, 2p12): Involvesmutation in the translation initiation factor EIF2AK3.The recessive disorder affects neonatal or infantileinsulin-dependent diabetes. Later, bone defects (epiph-yseal dysplasia, osteoporosis), retarded growth, liverand kidney malfunction, mental retardation and heartdisease may complicate the condition. ▶EIF2

Wolf: (Canis lupus, 2n = 78), a carnivorous mammal,which can form fertile hybrids with domesticateddogs (Canis familiaris, 2n = 78) as well as with thecoyote (C. latrans, 2n = 78) but not with foxes(Vulpes vulpes, 2n = 36). Domesticated dogs appearto be much closer evolutionarily to wolves (on thebasis of mtDNA) than to coyotes. ▶fox

Wolf-Hirschhorn Syndrome: A condition,which involvesdeletion (unequal crossing over, insertion) in one ofthe short arms of human chromosome 4p16.1 (usuallythe paternal) resulting in severe growth, mental, faceand genitalia defects, etc. The deletion generallyeliminates HOX7 (homeobox 7), responsible fornormal development in humans and mice. Hemi-zygosity for the gene is sufficient for the disease. Theseverity of the disease is affected by alteration atadjacent sites (Bergmann D et al 2005 Trends Genet21:188). ▶deletion, ▶hemizygous, ▶homeobox,▶homeotic genes, ▶Huntington’s chorea; Näf Det al 2001 Am J Hum Genet 10:91; Zollino M et al2003 Am J Hum Genet 72:590.

Wound Healing 2107

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Wolffian Ducts: Develop as a precursor of the malegonads of vertebrates. This development is enhancedunder the influence of testosterone hormone. Themale gonad (testes) is formed by the Sertoli cells thateventually surround the spermatogonia. The Leydigcells (Yao H-C et al 2002 Genes Dev 16:1433) secretethe steroid testosterone and the Sertoli cells producethe anti-Müllerian hormone (human chromosomallocation 12q13), which causes regression of theuterus and the Fallopian tubes.▶gonads,▶Müllerianducts, ▶DSS

Wolf-Parkinson-White Syndrome: A heart disease with ashort P and a long QRS phase of electrocardiography.It is also called preexcitation syndrome because theheart ventricles are excited prematurely. It may causeincreased palpitations and sudden death. The causesare complex; dominant defects at chromosome 7q3have been implicated and a mitochondrial componentmay also be involved. ▶electrocardiography, ▶mito-chondrial diseases in humans [Leber hereditary opticdystrophy].

Wolfram Syndrome (DIDMOAD): Mutation in humanchromosome 4p16.1 gene encoding a ~100 kDatransmembrane protein involves diabetes insipidus,diabetes mellitus, optic atrophy and deafness. It hasbeen proposed that a large mitochondrial deletionextending over several coding sequences (7.6 kb) isresponsible for these diseases but it has not beenconfirmed. ▶diabetes, ▶optic atrophy, ▶deafness,▶mitochondrial diseases in humans; Strom TM et al1998 Hum Mol Genet 7:2021.

Wolman Disease (lysosomal acid lipase deficiency):A condition due to autosomal recessive genes in thelong arm of human chromosome 10q24-q25 and inmouse chromosome 19. The early onset forms are dueto a deficiency of this enzyme (cholesteryl esterhydrolase) and are characterized by liver and spleenenlargement, failure to feed normally and death by theage of 2 to 4 months. The accumulation of cholesterolesters is caused by mutant alleles of the same locus. Insome forms survival is till the teens. ▶cholesterol,▶lysosomes, ▶lipase; Du H et al 1998 Hum. MolGenet 7:1347.

Woodchuck: ▶Marmota monax

Woodrats: There are many species mainly with 2n = 52.

Woods’ Light: Refers to an ultraviolet light source withnickel oxide filter and with a maximal transmission atabout 365 nm while most other spectral regions areblocked. ▶ultraviolet light

Woolly Hair: This may be black (and autosomaldominant) or blond (and autosomal recessive). Inboth cases, the hair is short and tightly curled.

Wordmatch: Finds exact matches of a given sizebetween two protein sequences. (http://ocgc.ca/programs/emboss/wordmatch.html).

Working Hypothesis: This is an experimentally testableassumption regarding a problem.

Worm Genetics: An informal reference to Caenorhab-ditis elegans. ▶Caenorhabditis

Woronin Bodies: These occur around fungal poressupposedly to protect against excessive leakage if thecells are damaged. (See Tenney K et al 2000 FungalGenet Biol 31:205).

Wortmannin: A protein from Penicillium fumiculosum/Talaromyces wortmanni which is a stimulator ofneutrophils and inhibitor of PIK, DNA-PK and thusinhibits the repair of double-breaks in the DNA (seeFig. W12). Wortmannin modulates the phosphatidy-linositol metabolic pathway. ▶neutrophil, ▶PIK,▶DNA-PK, ▶phosphatidylinositol; Wang H et al2001 Nucleic Acid Res 29:1653.

OCH3OCO

CH3

O

CH3OCH2

H3C

OO

O

12

5

1110

6

987

34

Figure W12. Wortmannin

Woude Syndrome: ▶van der Woude syndrome

Wound Healing: Requires angiogenesis, which can beprovided by administering angiogenic proteins suchas vascular endothelial growth factor (VEGF) orplacental growth factor. To ensure a stabilizing effect,the delivery of multiple growth factors may behelpful. Hypoxia-inducible factor (HIF) can stimulateangiogenesis. HIF-1 heterodimer has two subunits αand β. The former has an oxygen-sensitive degrada-tion domain (ODD). This domain is prolyl hydro-xylated in an oxygen-dependent manner and can bindthe von Hippel-Lindau protein and consequently theHIF-1α subunit is degraded by the proteasome undernormal oxygen tension. Under hypoxia, HIF-1α canheterodimerize with HIF-β and upon entering thenucleus it induces gene expression. The prevention ofHIF-α degradation or its overexpression results innuclear translocation and VEGF expression undernormal oxygen level. If the ODD domain is removed,VEGF and other genes are upregulated. In a speciallyengineered vector complex on a fibrin surgical matrix,entrapped in a DNA nanoparticle delivered to thedermal wound of mice resulted in potent therapeutic

2108 Wound-Healing Assay

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effects (Trentin D et al 2006 Proc Natl Acad Sci USA103:2506). The disruption of the epithelial cell layergenerates endogenous electric field and cell migra-tion. Phosphatidylinositol-3-OH kinase-γ and PTENgenes are essential for electrical signal-induced cellmigration and wound healing (Zhao M et al 2006Nature [Lond] 442:457). ▶tissue engineering,▶phosphoinositides, ▶PTEN, ▶von Hipple-Lindausyndrome, ▶VEGF, ▶angiogenesis

Wound-Healing Assay: Used to analyze cell migration.A confluent mammalian cell monolayer is scratchedby a blunt pipette tip and the “wound” so generatedheals by cell migration, which can be monitored byautomatic devices (TodaroGJ et al 1965 JCell Physiol66:325). It also detects the metastatic ability ofneoplasias (see Fig. W13). ▶metastasis, ▶neoplasia

Start 8 hrs 16 hours

Figure W13. Wound-healing time course

Wound Response: Upon wounding one leaf physiologi-cal changes take place in other parts of the plant bodyand the expression of proteinase inhibitors (Pin) istriggered by glycan, jasmonate and peptide signals.The 18-amino acid peptide signal, systemin, in tomatoplants, wounded by herbivorous insects, stimulatesproteinase expression. Salicylic acid may block thewound response.Wounding of plants may also inducea large number of genes of different function. Theplants may produce peroxides against the microbesinfecting the wounds. Phenolics may accumulate,photosynthesis may be reduced and ethylene biosyn-thesis may be induced. ▶glycan, ▶jasmonic acid,▶insect resistance in plants,▶host-pathogen relation-ship, ▶phenolics, ▶ethylene; Zhou L, Thornburg R1999, p 127. In: Reynolds PHS (Ed.) Inducible GeneExpression In Plants. CAB, New York.

Wrapping Choice: A generalized transducing phage“chooses” to scoop up the host rather than theviral DNA and “wraps” it into the phage capsid.▶transduction

Wright Blood Group: A very rare blood group; thefrequency of the Wr(a) antigen is about 3 × 10–4 inEurope. ▶blood groups

Wright-Fisher Model: ▶genetic drift, ▶drift genetic

Wrinkled/Smooth: This is a gene locus of pea, immorta-lized byMendel’s discovery ofmonogenic inheritance.The recessive “wrinkled allele” turned out to be an

insertional mutation.▶pea for photograph of wrinkledand smooth seeds.

Writhing Number: This indicates the contortion of aDNA double helix in a supercoiled state. It measuresthe helix axis in space. ▶linking number; KobayashiS et al 2001 Chem Pharm Bull Tokyo 49:1053.

Wrod Score (wrong lod score): Obtained when a linkageis estimated as lod scores on the assumption ofan incorrect genetic model (�). The genetic modelin complex traits may easily be misspecified. ▶lodscore, ▶mod score, ▶model genetic; Hodge SE,Elston RC 1994 Genet Epidemiol 11(4):329.

Wrongful Birth: Potential responsibilities of a physicianor a genetic counselor for negligence in informing orprenatal care of prospective parent(s) about risksinvolving childbirth. (See Randall KC 1979 HofstraLaw Rev 8:257).

Wrongful Life: A potential responsibility of parents,physicians and genetic counselors for not preventingthe birth of a child with a serious hereditary disease orin the case of illegitimacy, which may carry a socialstigma. The affected offspring may sue.▶counselinggenetic, ▶genetic privacy, ▶confidentiality, ▶pater-nity test; Foutz TK 1980 Tulane Law Rev 54:480.

WW Domain: A two-tyrosine motif (38–40 amino acids)of signaling proteins and a binding site for proline-rich peptides. The binding of a WW domain by Pin1and Nedd4 proteins apparently does not requireprolines for binding, rather the WW domains arebinding sites for phosphoserine and phosphothreo-nine. Among the many diverse proteins, their ligandsinclude Cdc25C phosphatase, microtubule associatedtau, carboxy-terminal of RNA polymerase II, etc.▶SH2, ▶SH3, ▶pleckstrin, ▶PTB, ▶signal transduc-tion, ▶Pin1; Nedd Sudol M, Hunter T 2000 Cell103:1001.

www (world wide web): The system is available throughthe Internet with the aid of a browser program, whichmakes possible the search through a computer linkedto the system. ▶Internet, ▶HTML

wx Gene (waxy): Occurs in various cereal plants and isused as a chromosome marker (in the short arm ofchromosome 9–56 of maize). In the presence of thedominant allele starch is formed (stained blue byiodine stain). If it is replaced by recessive allele,amylopectin is formed (stained red-brown) becauseof a defect in NDP-starch glucosyltransferase.▶iodine stain, ▶amylopectin, ▶TILLING

wx Gene 2109

Historical vignettes

Edith Kramer 2002 American J Art Therapy40(4):218

“How can we characterize [the opposite of kitsch]good art? Three elements seem essential; evocativepower, inner consistency, and an economy of meansso that the quality of the work would be diminishedif anything would be added or omitted.”

Apparent mutations were recorded by the ancientliterature. Aristotle says, “whoever does not resem-ble the parent is, in some respects, a monster,because in this case nature has deviated, to a certaindegree, from the hereditary type” (Generation ofAnimals, Book IV, Part 3, Para. 1).In 1844 WH Prescott retells the History of the

Conquest of Mexico (Dutton, New York): “I mustnot omit to notice a strange collection of humanmonsters, dwarfs, and other unfortunate persons, inwhose organization Nature had capriciously de-viated from her regular laws. Such hideousanomalies were regarded by the Aztecs as a suitableappendage of state. It is even said, they were insome cases the result of artificial means, employedby unnatural parents desirous to secure a provisionfor their offspring by thus qualifying them for aplace in the royal museum.”Thus even induced mutation had been anticipated

much before it had been experimentally demon-strated by HJ Muller and LJ Stadler in the mid1920s.

W