Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2003 Nov;165(3):1579–1586. doi: 10.1093/genetics/165.3.1579

Detecting population growth, selection and inherited fertility from haplotypic data in humans.

Frédéric Austerlitz 1, Luba Kalaydjieva 1, Evelyne Heyer 1
PMCID: PMC1462861  PMID: 14668404

Abstract

The frequency of a rare mutant allele and the level of allelic association between this allele and one or several closely linked markers are frequently measured in genetic epidemiology. Both quantities are related to the time elapsed since the appearance of the mutation in the population and the intrinsic growth rate of the mutation (which may be different from the average population growth rate). Here, we develop a method that uses these two kinds of genetic data to perform a joint estimation of the age of the mutation and the minimum growth rate that is compatible with its present frequency. In absence of demographic data, it provides a useful estimate of population growth rate. When such data are available, contrasts among estimates from several loci allow demographic processes, affecting all loci similarly, to be distinguished from selection, affecting loci differently. Testing these estimates on populations for which data are available for several disorders shows good congruence with demographic data in some cases whereas in others higher growth rates are obtained, which may be the result of selection or hidden demographic processes.

Full Text

The Full Text of this article is available as a PDF (95.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angelicheva D., Turnev I., Dye D., Chandler D., Thomas P. K., Kalaydjieva L. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter. Eur J Hum Genet. 1999 Jul;7(5):560–566. doi: 10.1038/sj.ejhg.5200319. [DOI] [PubMed] [Google Scholar]
  2. Austerlitz F., Heyer E. Allelic association is increased by correlation of effective family size. Eur J Hum Genet. 2000 Dec;8(12):980–985. doi: 10.1038/sj.ejhg.5200556. [DOI] [PubMed] [Google Scholar]
  3. Austerlitz F., Heyer E. Social transmission of reproductive behavior increases frequency of inherited disorders in a young-expanding population. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15140–15144. doi: 10.1073/pnas.95.25.15140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blumenfeld A., Slaugenhaupt S. A., Liebert C. B., Temper V., Maayan C., Gill S., Lucente D. E., Idelson M., MacCormack K., Monahan M. A. Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31. Am J Hum Genet. 1999 Apr;64(4):1110–1118. doi: 10.1086/302339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casaubon L. K., Melanson M., Lopes-Cendes I., Marineau C., Andermann E., Andermann F., Weissenbach J., Prévost C., Bouchard J. P., Mathieu J. The gene responsible for a severe form of peripheral neuropathy and agenesis of the corpus callosum maps to chromosome 15q. Am J Hum Genet. 1996 Jan;58(1):28–34. [PMC free article] [PubMed] [Google Scholar]
  6. Collins A., Morton N. E. Mapping a disease locus by allelic association. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1741–1745. doi: 10.1073/pnas.95.4.1741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dobbs DA, Vanhessche KP, Brazi E, Rautenstrauch V, V, Lenoir JY, Genêt JP, Wiles J, Bergens SH. Industrial Synthesis of (+)-cis-Methyl Dihydrojasmonate by Enantioselective Catalytic Hydrogenation; Identification of the Precatalyst. Angew Chem Int Ed Engl. 2000 Jun 2;39(11):1992–1995. doi: 10.1002/1521-3773(20000602)39:11<1992::aid-anie1992>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  8. Díaz A., Montfort M., Cormand B., Zeng B., Pastores G. M., Chabás A., Vilageliu L., Grinberg D. Gaucher disease: the N370S mutation in Ashkenazi Jewish and Spanish patients has a common origin and arose several thousand years ago. Am J Hum Genet. 1999 Apr;64(4):1233–1238. doi: 10.1086/302341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ellis N. A., Roe A. M., Kozloski J., Proytcheva M., Falk C., German J. Linkage disequilibrium between the FES, D15S127, and BLM loci in Ashkenazi Jews with Bloom syndrome. Am J Hum Genet. 1994 Sep;55(3):453–460. [PMC free article] [PubMed] [Google Scholar]
  10. Engert J. C., Bérubé P., Mercier J., Doré C., Lepage P., Ge B., Bouchard J. P., Mathieu J., Melançon S. B., Schalling M. ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet. 2000 Feb;24(2):120–125. doi: 10.1038/72769. [DOI] [PubMed] [Google Scholar]
  11. Goldstein D. B., Reich D. E., Bradman N., Usher S., Seligsohn U., Peretz H. Age estimates of two common mutations causing factor XI deficiency: recent genetic drift is not necessary for elevated disease incidence among Ashkenazi Jews. Am J Hum Genet. 1999 Apr;64(4):1071–1075. doi: 10.1086/302313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hunter Michael, Heyer Evelyne, Austerlitz Frederic, Angelicheva Dora, Nedkova Vania, Briones Paz, Gata Anna, de Pablo Rosaario, László Aranka, Bosshard Nills. The P28T mutation in the GALK1 gene accounts for galactokinase deficiency in Roma (Gypsy) patients across Europe. Pediatr Res. 2002 May;51(5):602–606. doi: 10.1203/00006450-200205000-00010. [DOI] [PubMed] [Google Scholar]
  13. Hästbacka J., de la Chapelle A., Kaitila I., Sistonen P., Weaver A., Lander E. Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat Genet. 1992 Nov;2(3):204–211. doi: 10.1038/ng1192-204. [DOI] [PubMed] [Google Scholar]
  14. Hästbacka J., de la Chapelle A., Mahtani M. M., Clines G., Reeve-Daly M. P., Daly M., Hamilton B. A., Kusumi K., Trivedi B., Weaver A. The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Cell. 1994 Sep 23;78(6):1073–1087. doi: 10.1016/0092-8674(94)90281-x. [DOI] [PubMed] [Google Scholar]
  15. Höglund P., Sistonen P., Norio R., Holmberg C., Dimberg A., Gustavson K. H., de la Chapelle A., Kere J. Fine mapping of the congenital chloride diarrhea gene by linkage disequilibrium. Am J Hum Genet. 1995 Jul;57(1):95–102. [PMC free article] [PubMed] [Google Scholar]
  16. Kalaydjieva L., Gresham D., Gooding R., Heather L., Baas F., de Jonge R., Blechschmidt K., Angelicheva D., Chandler D., Worsley P. N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. Am J Hum Genet. 2000 May 30;67(1):47–58. doi: 10.1086/302978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kalaydjieva L., Hallmayer J., Chandler D., Savov A., Nikolova A., Angelicheva D., King R. H., Ishpekova B., Honeyman K., Calafell F. Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24. Nat Genet. 1996 Oct;14(2):214–217. doi: 10.1038/ng1096-214. [DOI] [PubMed] [Google Scholar]
  18. Kalaydjieva L., Perez-Lezaun A., Angelicheva D., Onengut S., Dye D., Bosshard N. U., Jordanova A., Savov A., Yanakiev P., Kremensky I. A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am J Hum Genet. 1999 Nov;65(5):1299–1307. doi: 10.1086/302611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kaplan N. L., Hill W. G., Weir B. S. Likelihood methods for locating disease genes in nonequilibrium populations. Am J Hum Genet. 1995 Jan;56(1):18–32. [PMC free article] [PubMed] [Google Scholar]
  20. Labuda D., Zietkiewicz E., Labuda M. The genetic clock and the age of the founder effect in growing populations: a lesson from French Canadians and Ashkenazim. Am J Hum Genet. 1997 Sep;61(3):768–771. [PMC free article] [PubMed] [Google Scholar]
  21. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Motulsky A. G. Jewish diseases and origins. Nat Genet. 1995 Feb;9(2):99–101. doi: 10.1038/ng0295-99. [DOI] [PubMed] [Google Scholar]
  23. Pekkarinen P., Kestilä M., Paloneva J., Terwillign J., Varilo T., Järvi O., Hakola P., Peltonen L. Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium. Genomics. 1998 Dec 1;54(2):307–315. doi: 10.1006/geno.1998.5591. [DOI] [PubMed] [Google Scholar]
  24. Peltonen L., Jalanko A., Varilo T. Molecular genetics of the Finnish disease heritage. Hum Mol Genet. 1999;8(10):1913–1923. doi: 10.1093/hmg/8.10.1913. [DOI] [PubMed] [Google Scholar]
  25. Reeve Jeff P., Rannala Bruce. DMLE+: Bayesian linkage disequilibrium gene mapping. Bioinformatics. 2002 Jun;18(6):894–895. doi: 10.1093/bioinformatics/18.6.894. [DOI] [PubMed] [Google Scholar]
  26. Risch N., de Leon D., Ozelius L., Kramer P., Almasy L., Singer B., Fahn S., Breakefield X., Bressman S. Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nat Genet. 1995 Feb;9(2):152–159. doi: 10.1038/ng0295-152. [DOI] [PubMed] [Google Scholar]
  27. Rogers A. R., Harpending H. Population growth makes waves in the distribution of pairwise genetic differences. Mol Biol Evol. 1992 May;9(3):552–569. doi: 10.1093/oxfordjournals.molbev.a040727. [DOI] [PubMed] [Google Scholar]
  28. Sibert Alexandre, Austerlitz Frédéric, Heyer Evelyne. Wright-Fisher revisited: the case of fertility correlation. Theor Popul Biol. 2002 Sep;62(2):181–197. doi: 10.1006/tpbi.2002.1609. [DOI] [PubMed] [Google Scholar]
  29. Stephens J. C., Reich D. E., Goldstein D. B., Shin H. D., Smith M. W., Carrington M., Winkler C., Huttley G. A., Allikmets R., Schriml L. Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. Am J Hum Genet. 1998 Jun;62(6):1507–1515. doi: 10.1086/301867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. doi: 10.1093/genetics/123.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tremblay M., Vézina H. New estimates of intergenerational time intervals for the calculation of age and origins of mutations. Am J Hum Genet. 2000 Feb;66(2):651–658. doi: 10.1086/302770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Virtaneva K., Miao J., Träskelin A. L., Stone N., Warrington J. A., Weissenbach J., Myers R. M., Cox D. R., Sistonen P., de la Chapelle A. Progressive myoclonus epilepsy EPM1 locus maps to a 175-kb interval in distal 21q. Am J Hum Genet. 1996 Jun;58(6):1247–1253. [PMC free article] [PubMed] [Google Scholar]
  33. de la Chapelle A., Wright F. A. Linkage disequilibrium mapping in isolated populations: the example of Finland revisited. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12416–12423. doi: 10.1073/pnas.95.21.12416. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES