The Genom of Homo sapiens.pdf

PTC TASTE GENETICS 371the emergence of anatomically modern humans fromAfrica. Taking the non-taster phenotype as a model for adisease, this trait is consistent with the common disease/commonvariant hypothesis, which states that commonmedical disorders are the result of relatively ancientvariants that are now common in the population. This isin contrast to an alternative hypothesis, which suggeststhat common diseases are due to the cumulative effect ofmany different mutations, each of which is uncommonand has arisen more recently in the population. The PTCexample implies that many of the world’s predisposingdisease alleles are present in a fraction of the sub-SaharanAfrican population, and their spread into the rest of theworld may be accompanied by local genomic regions ofidentity by descent that can be used to fine-map and ultimatelyidentify these disease genes.ACKNOWLEDGMENTSWe thank the members of the Utah CEPH families andthe National Institutes of Health study population fortheir generous participation. We thank Brith Otterud,Kevin Cromer, and Tami Elsner for assistance in the geneticlinkage studies. This work was supported by theDivision of Intramural Research, the National Institute onDeafness and Other Communication Disorders, Z01-000046-04, by the National Human Genome Research Institute,T32 HG00044, by the W.M. Keck Foundation,and by the National Institute of General Medical Sciences.REFERENCESAdler E., Hoon M.A., Mueller K.L., Chandrashekar J., RybaN.J.P., and Zuker C.S. 2000. A novel family of mammaliantaste receptors. Cell 100: 693.Anonymous. 1931. Tasteblindness. Science 73: 14.Blakeslee A.F. 1931. Genetics of sensory thresholds: Taste forphenyl thio carbamide. Proc. Acad. Natl. Acad. Sci. 18: 120.Buck L. and Axel R. 1991. A novel multigene family may encodeodorant receptors: A molecular basis for odor recognition.Cell 65: 175.Chautard-Freire-Maia E.A. 1974. Linkage relationships between22 autosomal markers. Ann. Hum. Genet. 38: 191.Conneally P.M., Dumont-Driscoll M., Huntzinger R.S., NanceW.E., and Jackson C.E. 1976. Linkage relations of the loci forKell and phenylthiocarbamide taste sensitivity. Hum. Hered.26: 267.Dausset J., Cann H., Cohen D., Lathrop M., Lalouel J.-M., andWhite R. 1990. Centre d’etude du polymorphisme humain(CEPH): Collaborative mapping of the human genome. Genomics6: 575.Dib C., Faure S., Fizames C., Samson D., Drouot N., Vignal A.,Millasseau P., Marc S., Hazan J., Seboun E., Lathrop M.,Gyapay G., Morissette J., and Weissenbach J.A. 1996. Acomprehensive genetic map of the human genome based on5,264 microsatellites. Nature 380: 152.Drayna D., Coon H., Kim U.-K., Elsner T., Cromer K., OtterudB., Baird L., Peiffer A., and Leppert M. 2003. Genetic analysisof a complex trait in Utah Genetic Reference Project: Amajor locus for PTC taste ability on chromosome 7q and asecondary locus on chromosome 16p. Hum. Genet. 112:567.Guo S.-W. and Reed D. 2001. The genetics of phenylthiocarbamideperception. Ann. Hum. Biol. 28: 111.Kalmus H. 1958. Improvements in the classification of the tastergenotypes. Ann. Hum. Genet. 22: 222.NIH/CEPH Collaborative Mapping Group. 1992. A comprehensivegenetic linkage map of the human genome. Science 258:67.Olson J.M., Boehnke M., Neiswanger K., Roche A.F., and SiervogelR.M. 1989. Alternative genetic models for the inheritanceof the phenylthiocarbamide taste deficiency. Genet.Epidemiol. 6: 423.Reddy B.M. and Rao D.C. 1989. Phenylthiocarbamide taste sensitivityrevisited; complete sorting test supports residual familyresemblance. Genet. Epidemiol. 6: 413.Snyder L.H. 1931. Inherited taste deficiency. Science 74: 151.Spence M.A., Falk C.T., Neiswanger K., Field L.L., MarazitaM.L., Allen F.H., Siervogel R.M., Roche A.F., Crandall B.F.,and Sparkes R.S. 1984. Estimating the recombination frequencyfor the PTC-Kell linkage. Hum. Genet. 67: 183.Tepper B. 1998. 6-n-Propylthiouracil: A genetic marker fortaste, with implications for food preference and dietary habits.Am. J. Hum. Genet. 63: 1271.