Balancing selection on a recessive lethal deletion with pleiotropic effects on two neighboring genes in the porcine genome

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Livestock populations can be used to study recessive defects caused by deleterious alleles. The frequency of deleterious alleles including recessive lethal alleles can stay at high or moderate frequency within a population, especially if recessive lethal alleles exhibit an advantage for favourable traits in heterozygotes. In this study, we report such a recessive lethal deletion of 212kb (del) within the BBS9 gene in a breeding population of pigs. The deletion produces a truncated BBS9 protein expected to cause a complete loss-of-function, and we find a reduction of approximately 20% on the total number of piglets born from carrier by carrier matings. Homozygous del/del animals die mid- to late-gestation, as observed from high increase in numbers of mummified piglets resulting from carrier-by-carrier crosses. The moderate 10.8% carrier frequency (5.4% allele frequency) in this pig population suggests an advantage on a favourable trait in heterozygotes. Indeed, heterozygous carriers exhibit increased growth rate, an important selection trait in pig breeding. Increased growth and appetite together with a lower birth weight for carriers of the BBS9 null allele in pigs is analogous to the phenotype described in human and mouse for (naturally occurring) BBS9 null-mutants. We show that fetal death, however, is induced by reduced expression of the downstream BMPER gene, an essential gene for normal foetal development. In conclusion, this study describes a lethal 212kb deletion with pleiotropic effects on two different genes, one resulting in fetal death in homozygous state (BMPER), and the other increasing growth (BBS9) in heterozygous state. We provide strong evidence for balancing selection resulting in an unexpected high frequency of a lethal allele in the population. This study shows that the large amounts of genomic and phenotypic data routinely generated in modern commercial breeding programs deliver a powerful tool to monitor and control lethal alleles much more efficiently.

Original languageEnglish
Article numbere1007661
Number of pages20
JournalPlos Genetics
Volume14
Issue number9
DOIs
Publication statusPublished - 19 Sep 2018

Fingerprint

Lethal Genes
lethal genes
allele
Swine
genome
Genome
swine
gene
alleles
Breeding
pig
Fetal Death
Population
Genes
Heterozygote
genes
Gene Frequency
fetal death
Growth
Alleles

Cite this

@article{3c83e16e94fc4f9d8607d85c11475fd8,
title = "Balancing selection on a recessive lethal deletion with pleiotropic effects on two neighboring genes in the porcine genome",
abstract = "Livestock populations can be used to study recessive defects caused by deleterious alleles. The frequency of deleterious alleles including recessive lethal alleles can stay at high or moderate frequency within a population, especially if recessive lethal alleles exhibit an advantage for favourable traits in heterozygotes. In this study, we report such a recessive lethal deletion of 212kb (del) within the BBS9 gene in a breeding population of pigs. The deletion produces a truncated BBS9 protein expected to cause a complete loss-of-function, and we find a reduction of approximately 20{\%} on the total number of piglets born from carrier by carrier matings. Homozygous del/del animals die mid- to late-gestation, as observed from high increase in numbers of mummified piglets resulting from carrier-by-carrier crosses. The moderate 10.8{\%} carrier frequency (5.4{\%} allele frequency) in this pig population suggests an advantage on a favourable trait in heterozygotes. Indeed, heterozygous carriers exhibit increased growth rate, an important selection trait in pig breeding. Increased growth and appetite together with a lower birth weight for carriers of the BBS9 null allele in pigs is analogous to the phenotype described in human and mouse for (naturally occurring) BBS9 null-mutants. We show that fetal death, however, is induced by reduced expression of the downstream BMPER gene, an essential gene for normal foetal development. In conclusion, this study describes a lethal 212kb deletion with pleiotropic effects on two different genes, one resulting in fetal death in homozygous state (BMPER), and the other increasing growth (BBS9) in heterozygous state. We provide strong evidence for balancing selection resulting in an unexpected high frequency of a lethal allele in the population. This study shows that the large amounts of genomic and phenotypic data routinely generated in modern commercial breeding programs deliver a powerful tool to monitor and control lethal alleles much more efficiently.",
author = "Derks, {Martijn F.L.} and Lopes, {Marcos S.} and Mirte Bosse and Ole Madsen and Bert Dibbits and Barbara Harlizius and Groenen, {Martien A.M.} and Megens, {Hendrik Jan}",
year = "2018",
month = "9",
day = "19",
doi = "10.1371/journal.pgen.1007661",
language = "English",
volume = "14",
journal = "Plos Genetics",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "9",

}

Balancing selection on a recessive lethal deletion with pleiotropic effects on two neighboring genes in the porcine genome. / Derks, Martijn F.L.; Lopes, Marcos S.; Bosse, Mirte; Madsen, Ole; Dibbits, Bert; Harlizius, Barbara; Groenen, Martien A.M.; Megens, Hendrik Jan.

In: Plos Genetics, Vol. 14, No. 9, e1007661, 19.09.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Balancing selection on a recessive lethal deletion with pleiotropic effects on two neighboring genes in the porcine genome

AU - Derks, Martijn F.L.

AU - Lopes, Marcos S.

AU - Bosse, Mirte

AU - Madsen, Ole

AU - Dibbits, Bert

AU - Harlizius, Barbara

AU - Groenen, Martien A.M.

AU - Megens, Hendrik Jan

PY - 2018/9/19

Y1 - 2018/9/19

N2 - Livestock populations can be used to study recessive defects caused by deleterious alleles. The frequency of deleterious alleles including recessive lethal alleles can stay at high or moderate frequency within a population, especially if recessive lethal alleles exhibit an advantage for favourable traits in heterozygotes. In this study, we report such a recessive lethal deletion of 212kb (del) within the BBS9 gene in a breeding population of pigs. The deletion produces a truncated BBS9 protein expected to cause a complete loss-of-function, and we find a reduction of approximately 20% on the total number of piglets born from carrier by carrier matings. Homozygous del/del animals die mid- to late-gestation, as observed from high increase in numbers of mummified piglets resulting from carrier-by-carrier crosses. The moderate 10.8% carrier frequency (5.4% allele frequency) in this pig population suggests an advantage on a favourable trait in heterozygotes. Indeed, heterozygous carriers exhibit increased growth rate, an important selection trait in pig breeding. Increased growth and appetite together with a lower birth weight for carriers of the BBS9 null allele in pigs is analogous to the phenotype described in human and mouse for (naturally occurring) BBS9 null-mutants. We show that fetal death, however, is induced by reduced expression of the downstream BMPER gene, an essential gene for normal foetal development. In conclusion, this study describes a lethal 212kb deletion with pleiotropic effects on two different genes, one resulting in fetal death in homozygous state (BMPER), and the other increasing growth (BBS9) in heterozygous state. We provide strong evidence for balancing selection resulting in an unexpected high frequency of a lethal allele in the population. This study shows that the large amounts of genomic and phenotypic data routinely generated in modern commercial breeding programs deliver a powerful tool to monitor and control lethal alleles much more efficiently.

AB - Livestock populations can be used to study recessive defects caused by deleterious alleles. The frequency of deleterious alleles including recessive lethal alleles can stay at high or moderate frequency within a population, especially if recessive lethal alleles exhibit an advantage for favourable traits in heterozygotes. In this study, we report such a recessive lethal deletion of 212kb (del) within the BBS9 gene in a breeding population of pigs. The deletion produces a truncated BBS9 protein expected to cause a complete loss-of-function, and we find a reduction of approximately 20% on the total number of piglets born from carrier by carrier matings. Homozygous del/del animals die mid- to late-gestation, as observed from high increase in numbers of mummified piglets resulting from carrier-by-carrier crosses. The moderate 10.8% carrier frequency (5.4% allele frequency) in this pig population suggests an advantage on a favourable trait in heterozygotes. Indeed, heterozygous carriers exhibit increased growth rate, an important selection trait in pig breeding. Increased growth and appetite together with a lower birth weight for carriers of the BBS9 null allele in pigs is analogous to the phenotype described in human and mouse for (naturally occurring) BBS9 null-mutants. We show that fetal death, however, is induced by reduced expression of the downstream BMPER gene, an essential gene for normal foetal development. In conclusion, this study describes a lethal 212kb deletion with pleiotropic effects on two different genes, one resulting in fetal death in homozygous state (BMPER), and the other increasing growth (BBS9) in heterozygous state. We provide strong evidence for balancing selection resulting in an unexpected high frequency of a lethal allele in the population. This study shows that the large amounts of genomic and phenotypic data routinely generated in modern commercial breeding programs deliver a powerful tool to monitor and control lethal alleles much more efficiently.

U2 - 10.1371/journal.pgen.1007661

DO - 10.1371/journal.pgen.1007661

M3 - Article

VL - 14

JO - Plos Genetics

JF - Plos Genetics

SN - 1553-7404

IS - 9

M1 - e1007661

ER -