{"id":9241,"date":"2026-04-07T13:00:44","date_gmt":"2026-04-07T13:00:44","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/martijn-derks\/"},"modified":"2026-04-23T08:18:54","modified_gmt":"2026-04-23T08:18:54","slug":"martijn-derks","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/martijn-derks\/","title":{"rendered":"Martijn Derks"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":13419,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-9241","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"From Sequence to Phenotype","samenvatting":"Er is geen Nederlandse samenvatting beschikbaar. De Engelse samenvatting vind je <a href=\"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/martijn-derks\/\">hier<\/a>.","summary":"The DNA provides a blueprint of life containing the instruction, together with the environment, that determine the phenotype. In this thesis I attempt to further close the genotype phenotype gap in livestock, contributing to our understanding of important variation in the animals genomes. I analysed hundred thousands of genotypes, and hundreds of whole genome sequenced individuals to identify variation with impact, either deleterious (e.g. recessive lethals) or variants with positive effects on important selection traits. With this thesis I provide a comprehensive overview high-impact variation in various livestock breeds, and discuss the implications for breeding.\n\nIn chapter 2 I perform a survey to assess deleterious haplotypes that likely harbor a recessive lethal allele in three pig populations. I demonstrate that the approach to identify recessive lethal haplotypes from regions that show a deficit in homozygosity can successfully be applied in pigs. Moreover, I report one haplotype that results in relatively late termination of fetal development leading to mummification of homozygous animals.\n\nChapter 3 describes a sequence-based GWAS study to investigate the molecular basis of the sex-linked feathering rate at hatch in domestic turkey. I describe a 5-bp frameshift deletion in the prolactin receptor (PRLR) gene that is responsible for slow feathering at hatch. The consequence, a partial C-terminal loss of the prolactin receptor, is strikingly similar to the protein encoded by the slow feathering K allele in chicken, but with a different causative mutation.\n\nIn chapter 4 I examined the genome of commercial purebred chicken lines for deleterious and functional variations, combining genotype and whole-genome sequence data. I provide a genomic perspective on deleterious and functional genetic variation in three egg-laying breeds, giving insight into the process of purifying selection, and the role of recombination for breeds under strong artificial selection. In addition, we report multiple putative functional coding variants in selective sweep regions, which are likely under positive selection.\n\nIn chapter 5 I describe a unique example of allelic pleiotropy for a large deletion affecting two different genes in pigs. The deletion produces a truncated BBS9 protein, which subsequently results in enhanced growth rates in carrier animals. Intriguingly, a loss of function of this gene in human and mice leads to obesity. We show that fetal death in homozygotes, however, is not caused by an impaired BBS9 gene, but by reduced expression of the downstream BMPER gene, an essential gene for normal foetal development. Finally, we provide strong evidence for balancing selection, given a higher selection index for carrier animals, resulting in an unexpected high frequency of this lethal allele in the population.\n\nChapter 6 describes loss of function mutations in essential genes that cause embryonic lethality in pigs, decreasing litter sizes by 15.1 to 21.6% in carrier-by-carrier matings. I first reflect on the effect of genetic drift on lethal recessive variants, showing that lethal alleles can reach allele frequencies up to 10% (20% carrier frequency) by genetic drift alone. Next, I describe in detail the loss-of-function mutations that impair essential genes leading to embryonic lethality in homozygous embryos. The causal mutations are of different type including two splice-site variants (affecting POLRNB and TADA2A genes), one frameshift (URBN), and one missense (PNKP) variant. Finally, I describe the impact of the lethals on population fitness, and its role in the heterosis effect observed for crossbred litters.\n\nIn chapter 7 I describe a recessive 16-bp deletion in the SPTBN4 gene causing severe myopathy and postnatal mortality in pigs. The deletion induces a frameshift and a premature stop codon, producing an impaired and truncated spectrin beta non-erythrocytic 4 protein (SPTBN4). The affected piglets are unable to walk and die within 24 hours after birth. This study shows how the growing resources of genomics data can aid in the identification of variants that result in piglet mortality, and lead to the subsequent prevention of carrier-by-carrier crosses. Finally, I aim to increase awareness among breeders and farmers of \u201chidden\u201d genetic defects in the population, which helps to identify rare syndromes in breeding populations in the future.\n\nFinally, in chapter 8 I provide a framework to pinpoint likely causal variation and genes underlying important phenotypes in pigs. The variant prioritization method relies on the pig Combined Annotation Dependent Depletion (pCADD) scores, a machine learning method that provides impact scores to any possible substitution in the pig genome. I demonstrate the efficacy of the tool by reporting known and novel causal variants, of which many affect (non-coding) regulatory sequences associated with important phenotypes in pigs. Finally, the identified causal variants can be applied in breeding to improve genomic prediction.","auteur":"Martijn Derks","auteur_slug":"martijn-derks","publicatiedatum":"2 september 2020","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/martijnderks?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604071258","isbn":"978-94-6395-320-7","doi_nummer":"","naam_universiteit":"Wageningen University","afbeeldingen":13419,"naam_student:":"","binnenwerk":"","universiteit":"Wageningen University","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9241","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=9241"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9241\/revisions"}],"predecessor-version":[{"id":9242,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/9241\/revisions\/9242"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/13419"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=9241"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=9241"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}