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On the use of the transmission disequilibrium test to detect pseudo‐autosomal variants affecting traits with sex‐limited expression
Author(s) -
Elansary Mahmoud,
Stinckens Anneleen,
Ahariz Naima,
Cambisano Nadine,
Coppieters Wouter,
Grindflek Eli,
Son Maren,
Buys Nadine,
Georges Michel
Publication year - 2015
Publication title -
animal genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 81
eISSN - 1365-2052
pISSN - 0268-9146
DOI - 10.1111/age.12296
Subject(s) - biology , transmission disequilibrium test , linkage disequilibrium , genetics , locus (genetics) , single nucleotide polymorphism , allele , population , disequilibrium , genotype , sire , microsatellite , allele frequency , gene , demography , medicine , zoology , sociology , ophthalmology
Summary We herein describe the realization of a genome‐wide association study for scrotal hernia and cryptorchidism in Norwegian and Belgian commercial pig populations. We have used the transmission disequilibrium test to avoid spurious associations due to population stratification. By doing so, we obtained genome‐wide significant signals for both diseases with SNP s located in the pseudo‐autosomal region in the vicinity of the pseudo‐autosomal boundary. By further analyzing these signals, we demonstrate that the observed transmission disequilibria are artifactual. We determine that transmission bias at pseudo‐autosomal markers will occur (i) when analyzing traits with sex‐limited expression and (ii) when the allelic frequencies at the marker locus differ between X and Y chromosomes. We show that the bias is due to the fact that (i) sires will preferentially transmit the allele enriched on the Y (respectively X) chromosome to affected sons (respectively daughters) and (ii) dams will appear to preferentially transmit the allele enriched on the Y (respectively X) to affected sons (respectively daughters), as offspring inheriting the other allele are more likely to be non‐informative. We define the conditions to mitigate these issues, namely by (i) extracting information from maternal meiosis only and (ii) ignoring trios for which sire and dam have the same heterozygous genotype. We show that by applying these rules to scrotal hernia and cryptorchidism, the pseudo‐autosomal signals disappear, confirming their spurious nature.