Loss of function mutations in essential genes cause embryonic lethality in pigs

Martijn F.L. Derks, Arne B. Gjuvsland, Mirte Bosse, Marcos S. Lopes, Maren van Son, Barbara Harlizius, Beatrice F. Tan, Hanne Hamland, Eli Grindflek, Martien A.M. Groenen, Hendrik Jan Megens

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Lethal recessive alleles cause pre- or postnatal death in homozygous affected individuals, reducing fertility. Especially in small size domestic and wild populations, those alleles might be exposed by inbreeding, caused by matings between related parents that inherited the same recessive lethal allele from a common ancestor. In this study we report five relatively common (up to 13.4% carrier frequency) recessive lethal haplotypes in two commercial pig populations. The lethal haplotypes have a large effect on carrier-by-carrier matings, decreasing litter sizes by 15.1 to 21.6%. The causal mutations are of different type including two splice-site variants (affecting POLR1B and TADA2A genes), one frameshift (URB1), and one missense (PNKP) variant, resulting in a complete loss-of-function of these essential genes. The recessive lethal alleles affect up to 2.9% of the litters within a single population and are responsible for the death of 0.52% of the total population of embryos. Moreover, we provide compelling evidence that the identified embryonic lethal alleles contribute to the observed heterosis effect for fertility (i.e. larger litters in crossbred offspring). Together, this work marks specific recessive lethal variation describing its functional consequences at the molecular, phenotypic, and population level, providing a unique model to better understand fertility and heterosis in livestock.

LanguageEnglish
Pagese1008055
JournalPlos Genetics
Volume15
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019

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Lethal Genes
Essential Genes
lethal genes
pig
mutation
allele
Swine
Mutation
swine
gene
Hybrid Vigor
Fertility
fertility
heterosis
alleles
Population
Haplotypes
litter
litters (young animals)
Litter Size

Cite this

Derks, Martijn F.L. ; Gjuvsland, Arne B. ; Bosse, Mirte ; Lopes, Marcos S. ; van Son, Maren ; Harlizius, Barbara ; Tan, Beatrice F. ; Hamland, Hanne ; Grindflek, Eli ; Groenen, Martien A.M. ; Megens, Hendrik Jan. / Loss of function mutations in essential genes cause embryonic lethality in pigs. In: Plos Genetics. 2019 ; Vol. 15, No. 3. pp. e1008055.
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Derks, MFL, Gjuvsland, AB, Bosse, M, Lopes, MS, van Son, M, Harlizius, B, Tan, BF, Hamland, H, Grindflek, E, Groenen, MAM & Megens, HJ 2019, 'Loss of function mutations in essential genes cause embryonic lethality in pigs', Plos Genetics, vol. 15, no. 3, pp. e1008055. https://doi.org/10.1371/journal.pgen.1008055

Loss of function mutations in essential genes cause embryonic lethality in pigs. / Derks, Martijn F.L.; Gjuvsland, Arne B.; Bosse, Mirte; Lopes, Marcos S.; van Son, Maren; Harlizius, Barbara; Tan, Beatrice F.; Hamland, Hanne; Grindflek, Eli; Groenen, Martien A.M.; Megens, Hendrik Jan.

In: Plos Genetics, Vol. 15, No. 3, 01.03.2019, p. e1008055.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Loss of function mutations in essential genes cause embryonic lethality in pigs

AU - Derks, Martijn F.L.

AU - Gjuvsland, Arne B.

AU - Bosse, Mirte

AU - Lopes, Marcos S.

AU - van Son, Maren

AU - Harlizius, Barbara

AU - Tan, Beatrice F.

AU - Hamland, Hanne

AU - Grindflek, Eli

AU - Groenen, Martien A.M.

AU - Megens, Hendrik Jan

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N2 - Lethal recessive alleles cause pre- or postnatal death in homozygous affected individuals, reducing fertility. Especially in small size domestic and wild populations, those alleles might be exposed by inbreeding, caused by matings between related parents that inherited the same recessive lethal allele from a common ancestor. In this study we report five relatively common (up to 13.4% carrier frequency) recessive lethal haplotypes in two commercial pig populations. The lethal haplotypes have a large effect on carrier-by-carrier matings, decreasing litter sizes by 15.1 to 21.6%. The causal mutations are of different type including two splice-site variants (affecting POLR1B and TADA2A genes), one frameshift (URB1), and one missense (PNKP) variant, resulting in a complete loss-of-function of these essential genes. The recessive lethal alleles affect up to 2.9% of the litters within a single population and are responsible for the death of 0.52% of the total population of embryos. Moreover, we provide compelling evidence that the identified embryonic lethal alleles contribute to the observed heterosis effect for fertility (i.e. larger litters in crossbred offspring). Together, this work marks specific recessive lethal variation describing its functional consequences at the molecular, phenotypic, and population level, providing a unique model to better understand fertility and heterosis in livestock.

AB - Lethal recessive alleles cause pre- or postnatal death in homozygous affected individuals, reducing fertility. Especially in small size domestic and wild populations, those alleles might be exposed by inbreeding, caused by matings between related parents that inherited the same recessive lethal allele from a common ancestor. In this study we report five relatively common (up to 13.4% carrier frequency) recessive lethal haplotypes in two commercial pig populations. The lethal haplotypes have a large effect on carrier-by-carrier matings, decreasing litter sizes by 15.1 to 21.6%. The causal mutations are of different type including two splice-site variants (affecting POLR1B and TADA2A genes), one frameshift (URB1), and one missense (PNKP) variant, resulting in a complete loss-of-function of these essential genes. The recessive lethal alleles affect up to 2.9% of the litters within a single population and are responsible for the death of 0.52% of the total population of embryos. Moreover, we provide compelling evidence that the identified embryonic lethal alleles contribute to the observed heterosis effect for fertility (i.e. larger litters in crossbred offspring). Together, this work marks specific recessive lethal variation describing its functional consequences at the molecular, phenotypic, and population level, providing a unique model to better understand fertility and heterosis in livestock.

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DO - 10.1371/journal.pgen.1008055

M3 - Article

VL - 15

SP - e1008055

JO - Plos Genetics

T2 - Plos Genetics

JF - Plos Genetics

SN - 1553-7404

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ER -