From sequence to phenotype: the impact of deleterious variation in livestock

Abstract

2-A systematic survey to identify lethal recessive variation in highly managed pig populations 3-Early and late feathering in turkey and chicken: same gene but different mutations 4-A survey of functional genomic variation in domesticated chickens 5-Balancing selection on a recessive lethal deletion with pleiotropic effects on two neighboring genes in the porcine genome 6-Loss of function mutations in essential genes cause embryonic lethality in pigs 7-Detection of a frameshift deletion in the SPTBN4 gene leads to prevention of severe myopathy and postnatal mortality in pigs 8-Accelerated discovery of functional variation in pigs 9-General discussion References Summary Curriculum Vitae Acknowledgements 1 General introduction 13 1.3 Deleterious alleles In animal breeding and genomics we try to predict the effect of specific genetic variants on the phenotype or performance of farm animals. The genetic variants can usually be classified in three categories (though context-dependent): (1) Variants with positive effects; (2) variants that are benign (neutral); and (3) variants with deleterious effects. With the emergence of noticeable genetic defects and a decline Glossary SNP: Single nucleotide polymorphism, resulting in another nucleotide at one single base in the genome. Indel: Small deletion or insertion of bases in the genome. Haplotype: A group of alleles in an organism that are inherited together from a single parent. Genetic drift: The random fluctuations of allele frequencies from generation to generation. Mutation load: The total genetic burden in a population resulting from accumulated deleterious mutations Recessive lethal: A variant resulting in a lethal phenotype in homozygous state (two copies of the variant) SNP array: A type of DNA microarray which is used to detect polymorphisms within a population WGS: Whole genome sequence Effective population size: The number of individuals in a population who contribute offspring to the next generation LoF variant: A variant that lead to a loss of function of a gene and the associated protein. Missense variant: A point mutation in which a single nucleotide change results in a codon that codes for a different amino acid