A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle

Terhi Iso-Touru, Christine Wurmser, Heli Venhoranta, Maya Hiltpold, Tujia Savolainen, Anu Sironen, Konrad Fischer, Krzysztof Flisikowski, Ruedi Fries, Alejandro Vicente-Carrillo, Manuel Alvarez-Rodriguez, S. Nagy, Mervi Mutikainen, Jaana Peippo, Juhani Taponen, Goutam Sahana, Bernt Guldbrandtsen, Henri Simonen, Heriberto Rodriguez-Martinez, Magnus AnderssonHubert Pausch

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected. Results: Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P = 0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5′ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle. Conclusions: Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).

Original languageEnglish
Article number286
JournalBMC genomics
Volume20
Issue number1
DOIs
Publication statusPublished - Apr 11 2019

Fingerprint

RNA Splice Sites
Sperm Tail
Alleles
Haplotypes
Spermatozoa
Artificial Insemination
Semen
Fertilization
Single Nucleotide Polymorphism
Chromosomes
Genotype
Mothers
Parturition
Genome
Databases
Mutation
Population
Genes
Proteins

Keywords

  • Cattle
  • CCDC189
  • Immotile sperm
  • Male infertility
  • Sterility

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Iso-Touru, T., Wurmser, C., Venhoranta, H., Hiltpold, M., Savolainen, T., Sironen, A., ... Pausch, H. (2019). A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle. BMC genomics, 20(1), [286]. https://doi.org/10.1186/s12864-019-5628-y

A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle. / Iso-Touru, Terhi; Wurmser, Christine; Venhoranta, Heli; Hiltpold, Maya; Savolainen, Tujia; Sironen, Anu; Fischer, Konrad; Flisikowski, Krzysztof; Fries, Ruedi; Vicente-Carrillo, Alejandro; Alvarez-Rodriguez, Manuel; Nagy, S.; Mutikainen, Mervi; Peippo, Jaana; Taponen, Juhani; Sahana, Goutam; Guldbrandtsen, Bernt; Simonen, Henri; Rodriguez-Martinez, Heriberto; Andersson, Magnus; Pausch, Hubert.

In: BMC genomics, Vol. 20, No. 1, 286, 11.04.2019.

Research output: Contribution to journalArticle

Iso-Touru, T, Wurmser, C, Venhoranta, H, Hiltpold, M, Savolainen, T, Sironen, A, Fischer, K, Flisikowski, K, Fries, R, Vicente-Carrillo, A, Alvarez-Rodriguez, M, Nagy, S, Mutikainen, M, Peippo, J, Taponen, J, Sahana, G, Guldbrandtsen, B, Simonen, H, Rodriguez-Martinez, H, Andersson, M & Pausch, H 2019, 'A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle', BMC genomics, vol. 20, no. 1, 286. https://doi.org/10.1186/s12864-019-5628-y
Iso-Touru T, Wurmser C, Venhoranta H, Hiltpold M, Savolainen T, Sironen A et al. A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle. BMC genomics. 2019 Apr 11;20(1). 286. https://doi.org/10.1186/s12864-019-5628-y
Iso-Touru, Terhi ; Wurmser, Christine ; Venhoranta, Heli ; Hiltpold, Maya ; Savolainen, Tujia ; Sironen, Anu ; Fischer, Konrad ; Flisikowski, Krzysztof ; Fries, Ruedi ; Vicente-Carrillo, Alejandro ; Alvarez-Rodriguez, Manuel ; Nagy, S. ; Mutikainen, Mervi ; Peippo, Jaana ; Taponen, Juhani ; Sahana, Goutam ; Guldbrandtsen, Bernt ; Simonen, Henri ; Rodriguez-Martinez, Heriberto ; Andersson, Magnus ; Pausch, Hubert. / A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle. In: BMC genomics. 2019 ; Vol. 20, No. 1.
@article{44c14ef48df243f9bc79610ff50d6e65,
title = "A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle",
abstract = "Background: Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected. Results: Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P = 0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5′ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40{\%}, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5{\%} in Nordic Red cattle. Conclusions: Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).",
keywords = "Cattle, CCDC189, Immotile sperm, Male infertility, Sterility",
author = "Terhi Iso-Touru and Christine Wurmser and Heli Venhoranta and Maya Hiltpold and Tujia Savolainen and Anu Sironen and Konrad Fischer and Krzysztof Flisikowski and Ruedi Fries and Alejandro Vicente-Carrillo and Manuel Alvarez-Rodriguez and S. Nagy and Mervi Mutikainen and Jaana Peippo and Juhani Taponen and Goutam Sahana and Bernt Guldbrandtsen and Henri Simonen and Heriberto Rodriguez-Martinez and Magnus Andersson and Hubert Pausch",
year = "2019",
month = "4",
day = "11",
doi = "10.1186/s12864-019-5628-y",
language = "English",
volume = "20",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle

AU - Iso-Touru, Terhi

AU - Wurmser, Christine

AU - Venhoranta, Heli

AU - Hiltpold, Maya

AU - Savolainen, Tujia

AU - Sironen, Anu

AU - Fischer, Konrad

AU - Flisikowski, Krzysztof

AU - Fries, Ruedi

AU - Vicente-Carrillo, Alejandro

AU - Alvarez-Rodriguez, Manuel

AU - Nagy, S.

AU - Mutikainen, Mervi

AU - Peippo, Jaana

AU - Taponen, Juhani

AU - Sahana, Goutam

AU - Guldbrandtsen, Bernt

AU - Simonen, Henri

AU - Rodriguez-Martinez, Heriberto

AU - Andersson, Magnus

AU - Pausch, Hubert

PY - 2019/4/11

Y1 - 2019/4/11

N2 - Background: Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected. Results: Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P = 0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5′ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle. Conclusions: Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).

AB - Background: Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected. Results: Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P = 0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5′ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle. Conclusions: Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).

KW - Cattle

KW - CCDC189

KW - Immotile sperm

KW - Male infertility

KW - Sterility

UR - http://www.scopus.com/inward/record.url?scp=85064220235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064220235&partnerID=8YFLogxK

U2 - 10.1186/s12864-019-5628-y

DO - 10.1186/s12864-019-5628-y

M3 - Article

C2 - 30975085

AN - SCOPUS:85064220235

VL - 20

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 286

ER -