Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Sep;73(3):516-23.
doi: 10.1086/378207. Epub 2003 Jul 29.

Estimation of the inbreeding coefficient through use of genomic data

Anne-Louise Leutenegger  1 , Bernard Prum, Emmanuelle Génin, Christophe Verny, Arnaud Lemainque, Françoise Clerget-Darpoux, Elizabeth A Thompson
Affiliations

Estimation of the inbreeding coefficient through use of genomic data

Anne-Louise Leutenegger et al. Am J Hum Genet. 2003 Sep.

Abstract

Many linkage studies are performed in inbred populations, either small isolated populations or large populations with a long tradition of marriages between relatives. In such populations, there exist very complex genealogies with unknown loops. Therefore, the true inbreeding coefficient of an individual is often unknown. Good estimators of the inbreeding coefficient (f) are important, since it has been shown that underestimation of f may lead to false linkage conclusions. When an individual is genotyped for markers spanning the whole genome, it should be possible to use this genomic information to estimate that individual's f. To do so, we propose a maximum-likelihood method that takes marker dependencies into account through a hidden Markov model. This methodology also allows us to infer the full probability distribution of the identity-by-descent (IBD) status of the two alleles of an individual at each marker along the genome (posterior IBD probabilities) and provides a variance for the estimates. We simulate a full genome scan mimicking the true autosomal genome for (1) a first-cousin pedigree and (2) a quadruple-second-cousin pedigree. In both cases, we find that our method accurately estimates f for different marker maps. We also find that the proportion of genome IBD in an individual with a given genealogy is very variable. The approach is illustrated with data from a study of demyelinating autosomal recessive Charcot-Marie-Tooth disease.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Quadruple-second-cousin pedigree (cyclic type)
Figure 2
Figure 2
Estimated f (formula image) versus marker IBD proportion (formula image) for offspring of first cousins under 1.67-cM SNP map with marker allele frequencies 0.4/0.6 (S1) (A), 5-cM microsatellite map with marker allele frequencies 0.2/0.2/0.2/0.2/0.2 (S2) (B), and 10-cM microsatellite map with marker allele frequencies 0.2/0.2/0.2/0.2/0.2 (S3) (C). The solid line represents formula image.
Figure 3
Figure 3
Estimated f (formula image) for the 26 individuals with CMT disease. Solid lines represent formula image. SEs were obtained from the observed Fisher information matrix with 8,000 Monte Carlo realizations. 1C+ = first-cousin offspring whose paternal grandparents are also first cousins; 1C = first-cousin offspring; 2C = second-cousin offspring; ? = no genealogical information. fg is the proportion of genome IBD expected from the genealogy.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

Electronic-Database Information

    1. Pangaea, http://www.stat.washington.edu/thompson/Genepi/pangaea.shtml (for the Genedrop and kin programs of the MORGAN2.5 software package)

References

    1. Abney M, Ober C, McPeek MS (2002) Quantitative-trait homozygosity and association mapping and empirical genomewide significance in large, complex pedigrees: fasting serum-insulin level in the Hutterites. Am J Hum Genet 70:920–934 - PMC - PubMed
    1. Baum LE (1972) An inequality and associated maximization technique in statistical estimation for probabilistic functions of Markov processes. Inequalities 3:1–8
    1. Baum LE, Petrie T, Soules G, Weiss N (1970) A maximization technique occurring in the statistical analysis of probabilistic functions on Markov Chains. Ann Math Stat 41:164–171
    1. Boehnke M, Cox NJ (1997) Accurate inference of relationships in sib-pair linkage studies. Am J Hum Genet 61:423–429 - PMC - PubMed
    1. Bouche P, Gherardi R, Cathala HP, Lhermitte F, Castaigne P (1983) Peroneal muscular atrophy. Part 1. Clinical and electrophysiological study. J Neurol Sci 61:389–399 - PubMed

Publication types

LinkOut - more resources