Information on ancestry from genetic markers

It is possible to estimate the proportionate contributions of ancestral populations to admixed individuals or populations using genetic markers, but different loci and alleles vary considerably in the amount of information that they provide. Conventionally, the allele frequency difference between parental populations (δ) has been used as the criterion to select informative markers. However, it is unclear how to use δ for multiallelic loci, or populations formed by the mixture of more than two groups. Moreover, several other factors, including the actual ancestral proportions and the relative genetic diversities of the parental populations, affect the information provided by genetic markers. We demonstrate here that using δ as the sole criterion for marker selection is inadequate, and we propose, instead, to use Fisher's information, which is the inverse of the variance of the estimated ancestral contributions. This measure is superior because it is directly related to the precision of ancestry estimates. Although δ is related to Fisher's information, the relationship is neither linear nor simple, and the information can vary widely for markers with identical δs. Fortunately, Fisher's information is easily computed and formally extends to the situation of multiple alleles and/or parental populations. We examined the distribution of information for SNP and microsatellite loci available in the public domain for a variety of model admixed populations. The information, on average, is higher for microsatellite loci, but exceptional SNPs exceed the best microsatellites. Despite the large number of genetic markers that have been identified for admixture analysis, it appears that information for estimating admixture proportions is limited, and estimates will typically have wide confidence intervals. © 2004 Wiley‐Liss,Inc.

[1]  Li Jin,et al.  Skin pigmentation, biogeographical ancestry and admixture mapping , 2003, Human Genetics.

[2]  M. Feldman,et al.  Genetic Structure of Human Populations , 2002, Science.

[3]  S. Gabriel,et al.  The Structure of Haplotype Blocks in the Human Genome , 2002, Science.

[4]  F. Salzano,et al.  Unequal contributions of male and female gene pools from parental populations in the African descendants of the city of Melo, Uruguay. , 2002, American journal of physical anthropology.

[5]  Jonathan Scott Friedlaender,et al.  A Human Genome Diversity Cell Line Panel , 2002, Science.

[6]  Hongzhe Li,et al.  Ethnic-difference markers for use in mapping by admixture linkage disequilibrium. , 2002, American journal of human genetics.

[7]  S. O’Brien,et al.  Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations. , 2001, American journal of human genetics.

[8]  J. Stephens,et al.  Haplotype Variation and Linkage Disequilibrium in 313 Human Genes , 2001, Science.

[9]  James L. Weber,et al.  7 Genotyping for human whole-genome scans: Past, present, and future , 2001 .

[10]  E. Boerwinkle,et al.  Population structure in admixed populations: effect of admixture dynamics on the pattern of linkage disequilibrium. , 2001, American journal of human genetics.

[11]  R. Kittles,et al.  Ancestral proportions and admixture dynamics in geographically defined African Americans living in South Carolina. , 2001, American journal of physical anthropology.

[12]  John P. Rice,et al.  Genotyping for human whole-genome scans: past, present, and future. , 2001, Advances in genetics.

[13]  J. Stephens,et al.  Significant admixture linkage disequilibrium across 30 cM around the FY locus in African Americans. , 2000, American journal of human genetics.

[14]  J. Carpenter,et al.  Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African‐American populations , 2000, Annals of human genetics.

[15]  J. Long,et al.  Individual estimates of European genetic admixture associated with lower body-mass index, plasma glucose, and prevalence of type 2 diabetes in Pima Indians. , 2000, American journal of human genetics.

[16]  J. Carpenter,et al.  Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations. , 2000, Annals of human genetics.

[17]  D. Allison,et al.  Estimating African American admixture proportions by use of population-specific alleles. , 1998, American journal of human genetics.

[18]  P. McKeigue,et al.  Mapping genes that underlie ethnic differences in disease risk: methods for detecting linkage in admixed populations, by conditioning on parental admixture. , 1998, American journal of human genetics.

[19]  L. Jin,et al.  Ethnic-affiliation estimation by use of population-specific DNA markers. , 1997, American journal of human genetics.

[20]  D. Bing,et al.  Major histocompatibility complex class II alleles and haplotypes and blood groups of four Amerindian tribes of northern Colombia. , 1994, Human immunology.

[21]  J. Stephens,et al.  Polymorphic admixture typing in human ethnic populations. , 1994, American journal of human genetics.

[22]  J. Long,et al.  Genetic variation in Arizona Mexican Americans: estimation and interpretation of admixture proportions. , 1991, American journal of physical anthropology.

[23]  J. Long.  The genetic structure of admixed populations. , 1991, Genetics.

[24]  D. Rao,et al.  Relationship of prevalence of non‐insulin‐dependent diabetes mellitus to Amerindian admixture in the Mexican Americans of San Antonio, Texas , 1986, Genetic epidemiology.

[25]  Ranajit Chakraborty,et al.  Gene admixture in human populations: Models and predictions , 1986 .

[26]  S. Wright.  Evolution and the Genetics of Populations, Volume 3: Experimental Results and Evolutionary Deductions , 1977 .

[27]  T. Reed.  Number of Gene Loci required for Accurate Estimation of Ancestral Population Proportions in Individual Human Hybrids , 1973, Nature.

[28]  R. Ward,et al.  Admixture Studies and the Detection of Selection , 1973, Science.

[29]  R. Elston,et al.  The estimation of admixture in racial hybrids , 1971, Annals of human genetics.

[30]  N. Reid,et al.  Likelihood , 1993 .

[31]  T. E. Reed,et al.  Caucasian genes in American Negroes. , 1969, Science.

[32]  B. Glass,et al.  The dynamics of racial intermixture; an analysis based on the American Negro. , 1953, American journal of human genetics.

[33]  G. Dahlberg,et al.  Genetics of human populations. , 1948, Advances in genetics.