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ISSN : 1598-5504(Print)
ISSN : 2383-8272(Online)
Journal of Agriculture & Life Science Vol.55 No.2 pp.137-143

Exploration of OMIA Registered Recessive Mutations in Hanwoo Cattle

Devender Arora1†, Krishnamoorthy Srikanth1,2†, Dajeong Lim1, Jong-Eun Park1, Soyoung choi1, Seung-hwan Lee3, Dong-hyun Shin4, Won-choul Park1*
1Animal Genomics and Bioinformatics Division, National Institute of Animal Science, RDA, Wanju, 55365, Republic of Korea.
2Department of Animal Science, Cornell University, Ithaca, NY, United States-14853
3Department of Animal Science and Biotechnology, Chungnam National University, Daejeon, 34134, Republic of Korea
4Departments of Animal Biotechnology, Chonbuk National University, Jeonju, 54896, Republic of Korea

These authors contributed equally to this work.

*Corresponding author: Won-Cheoul Park Tel: +82-63-238-7317 Fax: +82-63-238-7347 E-mail:
November 5, 2020 ; January 8, 2021 ; April 1, 2021


Embryonic lethality due to recessive alleles is a major concern in livestock breeding programs. The Online Mendelian Inheritance in Animal (OMIA) is a database of reported recessive mutations in livestock that helps breeders to manage the segregation of these mutations in their population. Recessive alleles are lethal in the offspring of two carrier parents; therefore, identifying and eliminating carrier animals are critical for maintaining the breed. Hanwoo cattle is native to the Korean peninsula and is of great economic importance to Korea. Due to geographical constraints and the controlled breeding program with very few proven bulls, if not monitored periodically, the threat of segregation of recessive lethal alleles in the population remains high. Therefore, identifying potential carriers of lethal recessive alleles is critical in Hanwoo. In this regard, we genotyped 17,325 animals using bovine 50K Illumina SNP chip and also sequenced a further 311 animals which was mapped against the bovine reference genome sequence. We then used the OMIA database to identify reported recessive alleles and calculated the allele frequency of these mutations in the population to determine potential lethal alleles carried by the animals.


    Rural Development Administration(RDA)


    The fertility rate has an important role and attracts cow-calf-operators to raise beef cattle (Upperman et al., 2019). Embryonic survival is directly proportionate to the fertility rate of an organism, and hence, sustaining high embryonic survival remains a challenge in maintaining the overall population of an animal. (Diskin & Morris, 2008). A decrease in the calving rate correlates with the percentage of embryonic survival. A recent study tried to identify and explain the factors responsible for early embryonic death, death soon after birth, and semi-lethality with incomplete penetrance causing a reduced viability; additionally, it identified various haplotypes that carried putative recessive lethal and semi-lethal alleles along with their economic impact and linked with potential genetic causes in cattle (Jenko et al., 2019). Studies have indicated an alarming drop in fertilization: up to 55% in cattle leading to a decrease in the reproduction rate in many countries (Diskin & Morris, 2008). Intense breeding programs, strong selection for production traits, and their antagonistic relationship with reproduction have been identified as the main causes for such an outcome resulting in loss-of-function (LOF) alleles that required close monitoring at the genomics level to eliminate the factors responsible for LOF in essential genes (Liu et al., 2011;Derks et al., 2019). In this regard, several studies have successfully identified such recessive lethal alleles associated with functional loss at the genome wide level (Sahana et al., 2013;Derks et al., 2019;Jenko et al., 2019). Korean cattle (Hanwoo) is a breed raised mainly for beef pur- poses and has a high fertility rate (Park et al., 2013;Lopez et al., 2019). It is sought after for its excellent flavor profile due to its high intramuscular fat content (Bulik-Sullivan et al., 2015;Strucken et al., 2017). To sustain the demand for this meat, fertility and reproduction remains a key focus (Lee et al., 2014).

    Lethal alleles are the major concern having direct and indirect impacts on reproduction, and dealing with a recessive lethal allele itself is a challenge because the outcome is embryonic death when an embryo becomes homozygous, or there is a drastic impact when its effect is not fully expressed (Jenko et al., 2019). Among the reduced conception rates, longer calving intervals, or lower survival for live born animals are the alarming factors leading to reduce viability and reproduction (Fasquelle et al., 2009). Although lethal recessive alleles occur sporadically, with every generation, the probability of a carrier carrying them increases. Genotypic data enable us to identify the recessive carrier alleles, and recent studies have shown positive success in this direction by identifying such alleles in different breeds (Schulman et al., 2011;VanRaden et al., 2011;Hoff et al., 2017;Howard et al., 2017) and also identifying recessive alleles that impact fertility, longevity and the yield of their derivative (Fasquelle et al., 2009). Online Mendelian Inheritance in Animals (OMIA) is a curated, catalogued, comprehensive repository of identified recessive alleles in several livestock species (Lenffer et al., 2006). It consists of genetically determined characteristics possessed by organisms and has information from more than 135 animal species excluding humans and mouse with their OMIA ID representing first six digits for the respective trait/disorder and rest of the digits are the NCBI species taxonomy id.

    In Hanwoo, the geographically limited population and an intensive inbreeding program increase the probability of transmission of recessive lethal alleles to successive generations. Hence, monitoring and elimination of carrier mutants are critical processes. Therefore, we analyzed 17,325 SNP genotypic samples and 311 NGS animal samples for their recessive allele frequency against the OMIA database and reported the potential lethal alleles that could potentially impact the Hanwoo cattle fertility rate in coming generations (Nicholas, 2003;Lenffer et al., 2006).

    Materials and Methods

    Blood samples from Hanwoo were collected, and genomic DNA for genotyping assays was isolated using the DNeasy 96 Blood and tissue kit. DNA quantification was performed using NanoDrop, and the DNA samples of 17,325 Hanwoo cattle were submitted for genotyping. SNP genotyping was performed and imputed to higher densities using a large reference dataset of genotyped individuals with the 50k SNP Chip (Illumina Bovine SNP50 BeadChip; Illumina, San Diego, CA, version 2), and the 311 NGS data were used following the mapping on UMD3.1 (Langmead & Salzberg, 2012) with Bowtie v2. SNP identification was performed using the multi‐sample SNP‐calling procedure in the GATK package (https://www.broadinstitute. org/gatk) (Van der Auwera et al., 2013;Poplin et al., 2017). For the SNP Chip dataset, the phasing and imputation were done with Eagle and Minimac3 for the imputation (Browning & Browning, 2007;Howie et al., 2012) and have been reported previously (Hawlader et al., 2017;Bhuiyan et al., 2018). The accuracy of the imputation for the WGS was on average 78% for the SNPs with a minor allele frequency (MAF) > 0.01. Only SNPs that were located on the autosomal chromosomes (29 bovine chromosomes) were considered for the association analysis. The following quality control thresholds were considered: 1) SNPs that had a genotype call rate less than 90%, and 2) the p-values for Hardy-Weinberg equilibrium (HWE) = 1E-7, geno = 0.1, and mind = 0.1. Subsequently, reported lethal mutations were extracted from the SNP data using Plink1.9 (Purcell et al., 2007), and the allele frequencies of the major and minor alleles were identified (Fig. 1). Subsequently, an In-house database of recessive mutation alleles from the OMIA database ( were made and locally stored to map and identify lethal recessive alleles.

    Results and Discussion

    Identification of lethal alleles was done by analysis of the genomic data from haplotypes that are common in the same population but never occur in the homozygous state. Phenotypic expression of these lethal recessive alleles can cause prenatal death of homozygous offspring. The OMIA has catalogued 544 inherited mutations in cattle, out of which positional information and causal genes are listed for 103 mutations. Candidates with a homozygous lethal recessive allele genotype are assumed to be dead. Due to the small size of the NGS dataset, we did not see any new SNPs, and due to the low imputation accuracy, we mapped the allele information from the SNP Chip. Thus, subsequently, we mapped 45 SNPs with their positions in the respective chromosome. The analyses revealed that for OMIA 002033-9913, the mutational change from A>C in the CSN2 gene located at position 87,181,619 of chromosome 6 affects A2 milk. For OMIA ID 000214-9913, the mutation from A>T in the MITF gene at position 31,769,189 on chromosome 22 affects the coat color. For OMIA 001199-9913, the mutational effect on the MC1R gene affects the coat color, Recessive red at position 14,757,924 with a deleted mutation on chromosome 18 and OMIA 000963-9913 with a mutation in the LRP4 gene from C>T have a mutational effect on syndactyly (mule foot) found at position 77,675,440 of chromosome 15 and are segregating at a frequency of 24%, 20%, 8% and 3%, respectively. Because Hanwoo is mainly raised for beef purposes, and the identified recessive alleles have a mutational effect on A2 milk which can be seen as an alternative economical trait or the coat color which means it is not threatening to the Hanwoo population. Moreover, we have found an allele at position 20,922,527 of chromosome 5 related to Ehlers-Danlos syndrome followed by Ptosis on chromosome 17 but both have a comparatively low MAF in present generation but the associated risk cannot be ignored in coming generations and can be considered as a lethal recessive allele. Ehlers-Danlos syndrome is a heritable disorder related to connective tissue and is characterized by skin hyper-extensibility, fragility, and atrophic scarring. The mutant gene was identified as the EYPC gene which encodes collagen IV (Woodley et al., 1990). In an accumulation study, Knockout mouse was reported dead in absence of collagen IV at the embryonic stages (Marutani et al., 2004). Similarly, we have seen a mutational effect related to Pseudomyotonia disorder which has a root cause in muscular disorders (Sacchetto et al., 2009;Grunberg et al., 2010). Because pathogenic mutations rarely occur, chances remain high for a pleiotropic effect, and hence, close observation is required to monitor the MAF variation in the next generation. Similarly, we reported various locations and carrier frequencies for potential recessive alleles in the Hanwoo breed presented in Table 1.

    In this regard, a periodic surveillance program for monitoring congenital lethal mutations will be of great value to avoid the segregation of lethal mutations. These identified heterozygous alleles could help to monitor the genomic changes and MAF frequency for the next generation of data and enable us to better understand and observe the changing behavior of the MAF from generation to generation in a real time analysis.


    This work was supported by the AGENDA project (Project title: ‘Identification of genetic factors and biomarkers associated with pregnancy of Korean cattle (Hanwoo)’, Project No. PJ014826 of the National Institute of Animal Science, Rural Development Administration, Republic of Korea, and we acknowledge the Korean Institute of Animal Products Quality Evaluation (KAPE) for providing the samples. This study was supported by 2020 the RDA Fellowship Program of National Institute of Animal Science, Rural Development Administration, Republic of Korea



    Flow chart to identify recessive allele frequency in Hanwoo cattle.


    List of recessive alleles observed from OMIA database resource with Chromosomal position, Casual gene, MAF, Mutation, and mutational effect


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