RESUMO
MOTIVATION: In many situations, genome-wide association studies are performed in populations presenting stratification. Mixed models including a kinship matrix accounting for genetic relatedness among individuals have been shown to correct for population and/or family structure. Here we extend this methodology to generalized linear mixed models which properly model data under various distributions. In addition we perform association with ancestral haplotypes inferred using a hidden Markov model. RESULTS: The method was shown to properly account for stratification under various simulated scenari presenting population and/or family structure. Use of ancestral haplotypes resulted in higher power than SNPs on simulated datasets. Application to real data demonstrates the usefulness of the developed model. Full analysis of a dataset with 4600 individuals and 500 000 SNPs was performed in 2 h 36 min and required 2.28 Gb of RAM. AVAILABILITY: The software GLASCOW can be freely downloaded from www.giga.ulg.ac.be/jcms/prod_381171/software. CONTACT: francois.guillaume@jouy.inra.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Mapeamento Cromossômico/métodos , Biologia Computacional/métodos , Haplótipos , Modelos Lineares , Software , Animais , Bovinos , Simulação por Computador , Masculino , Cadeias de Markov , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We report the identification of a second loss-of-function mutation (c.1906T>C) in the bovine MRC2 gene causing the Crooked Tail Syndrome in Belgian Blue Cattle. We demonstrate that the ensuing substitution of the highly conserved Cysteine 636 with Arginine causes illegitimate receptor oligomerization, which is predicted to impair function of the MRC2 encoded protein, Endo180. We propose that this second MRC2 mutation was selected by breeders as a result of its favourable effect on muscularity in heterozygotes.
