Identification of Recently Selected Mutations Driven by Artificial Selection in Hanwoo (Korean Cattle)

Lim, Dajeong,Gondro, Cedric,Park, Hye Sun,Cho, Yong Min,Chai, Han Ha,Seong, Hwan Hoo,Yang, Bo Suk,Hong, Seong Koo,Chang, Won Kyung,Lee, Seung Hwan Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.5

Hanwoo have been subjected over the last seventy years to intensive artificial selection with the aim of improving meat production traits such as marbling and carcass weight. In this study, we performed a signature of selection analysis to identify recent positive selected regions driven by a long-term artificial selection process called a breeding program using whole genome SNP data. In order to investigate homozygous regions across the genome, we estimated iES (integrated Extended Haplotype Homozygosity SNP) for the each SNPs. As a result, we identified two highly homozygous regions that seem to be strong and/or recent positive selection. Five genes (DPH5, OLFM3, S1PR1, LRRN1 and CRBN) were included in this region. To go further in the interpretation of the observed signatures of selection, we subsequently concentrated on the annotation of differentiated genes defined according to the iES value of SNPs localized close or within them. We also described the detection of the adaptive evolution at the molecular level for the genes of interest. As a result, this analysis also led to the identification of OLFM3 as having a strong signal of selection in bovine lineage. The results of this study indicate that artificial selection which might have targeted most of these genes was mainly oriented towards improvement of meat production.

RESEARCH : Open Access ; Comparison of linkage disequilibrium levels in Iranian indigenous cattle using whole genome SNPs data

( Karim Karimi ),( Ali Esmailizadeh Koshkoiyeh ),( Cedric Gondro ) 한국동물자원과학회(구 한국축산학회) 2015 한국축산학회지 Vol.57 No.47

Background: Knowledge of linkage disequilibrium (LD) levels among different populations can be used to detect genetic diversity and to investigate the historical changes in population sizes. Availability of large numbers of SNP through new sequencing technologies has provided opportunities for extensive researches in quantifying LD patterns in cattle breeds. The aim of this study was to compare the extent of linkage disequilibrium among Iranian cattle breeds using high density SNP genotyping data. Results: A total of 70 samples, representing seven Iranian indigenous cattle breeds, were genotyped for 777962 SNPs.The average values of LD based on the r2 criterion were computed by grouping all syntenic SNP pairwises for intermarkerdistances from 0 Kb up to 1 Mb using three distance sets. Average r2 above 0.3 was observed at distances less than 30 Kb for Sistani and Kermani, 20 Kb for Najdi, Taleshi, Kurdi and Sarabi, and 10 Kb for Mazandarani. The LD levels were considerably different among the Iranian cattle breeds and the difference in LD extent was more detectable between the studied breeds at longer distances. Lower level of LD was observed for Mazandarani breed as compared to other breeds indicating larger ancestral population size in this breed. Kermani breed continued to have more slowly LD decay than all of the other breeds after 3 Kb distances. More slowly LD decay was observed in Kurdi and Sarabi breeds at larger distances (>100 Kb) showing that population decline has been more intense in more recent generations for these populations. Conclusions: A wide genetic diversity and different historical background were well reflected in the LD levels among Iranian cattle breeds. More LD fluctuation was observed in the shorter distances (less than 10 Kb) in different cattle populations. Despite of the sample size effects, High LD levels found in this study were in accordance with the presence of inbreeding and population decline in Iranian cattle breeds.

Characterization and Profiling of Liver microRNAs by RNA-sequencing in Cattle Divergently Selected for Residual Feed Intake

Al-Husseini, Wijdan,Chen, Yizhou,Gondro, Cedric,Herd, Robert M.,Gibson, John P.,Arthur, Paul F. Asian Australasian Association of Animal Productio 2016 Animal Bioscience Vol.29 No.10

MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally regulate expression of mRNAs in many biological pathways. Liver plays an important role in the feed efficiency of animals and high and low efficient cattle demonstrated different gene expression profiles by microarray. Here we report comprehensive miRNAs profiles by next-gen deep sequencing in Angus cattle divergently selected for residual feed intake (RFI) and identify miRNAs related to feed efficiency in beef cattle. Two microRNA libraries were constructed from pooled RNA extracted from livers of low and high RFI cattle, and sequenced by Illumina genome analyser. In total, 23,628,103 high quality short sequence reads were obtained and more than half of these reads were matched to the bovine genome (UMD 3.1). We identified 305 known bovine miRNAs. Bta-miR-143, bta-miR-30, bta-miR-122, bta-miR-378, and bta-let-7 were the top five most abundant miRNAs families expressed in liver, representing more than 63% of expressed miRNAs. We also identified 52 homologous miRNAs and 10 novel putative bovine-specific miRNAs, based on precursor sequence and the secondary structure and utilizing the miRBase (v. 21). We compared the miRNAs profile between high and low RFI animals and ranked the most differentially expressed bovine known miRNAs. Bovine miR-143 was the most abundant miRNA in the bovine liver and comprised 20% of total expressed mapped miRNAs. The most highly expressed miRNA in liver of mice and humans, miR-122, was the third most abundant in our cattle liver samples. We also identified 10 putative novel bovine-specific miRNA candidates. Differentially expressed miRNAs between high and low RFI cattle were identified with 18 miRNAs being up-regulated and 7 other miRNAs down-regulated in low RFI cattle. Our study has identified comprehensive miRNAs expressed in bovine liver. Some of the expressed miRNAs are novel in cattle. The differentially expressed miRNAs between high and low RFI give some insights into liver miRNAs regulating physiological pathways underlying variation in this measure of feed efficiency in bovines.

Comparison of linkage disequilibrium levels in Iranian indigenous cattle using whole genome SNPs data

Karimi, Karim,Koshkoiyeh, Ali Esmailizadeh,Gondro, Cedric Korean Society of Animal Sciences and Technology 2015 한국축산학회지 Vol.57 No.12

Background: Knowledge of linkage disequilibrium (LD) levels among different populations can be used to detect genetic diversity and to investigate the historical changes in population sizes. Availability of large numbers of SNP through new sequencing technologies has provided opportunities for extensive researches in quantifying LD patterns in cattle breeds. The aim of this study was to compare the extent of linkage disequilibrium among Iranian cattle breeds using high density SNP genotyping data. Results: A total of 70 samples, representing seven Iranian indigenous cattle breeds, were genotyped for 777962 SNPs. The average values of LD based on the $r^2$ criterion were computed by grouping all syntenic SNP pairwises for intermarker distances from 0 Kb up to 1 Mb using three distance sets. Average $r^2$ above 0.3 was observed at distances less than 30 Kb for Sistani and Kermani, 20 Kb for Najdi, Taleshi, Kurdi and Sarabi, and 10 Kb for Mazandarani. The LD levels were considerably different among the Iranian cattle breeds and the difference in LD extent was more detectable between the studied breeds at longer distances. Lower level of LD was observed for Mazandarani breed as compared to other breeds indicating larger ancestral population size in this breed. Kermani breed continued to have more slowly LD decay than all of the other breeds after 3 Kb distances. More slowly LD decay was observed in Kurdi and Sarabi breeds at larger distances (>100 Kb) showing that population decline has been more intense in more recent generations for these populations. Conclusions: A wide genetic diversity and different historical background were well reflected in the LD levels among Iranian cattle breeds. More LD fluctuation was observed in the shorter distances (less than 10 Kb) in different cattle populations. Despite of the sample size effects, High LD levels found in this study were in accordance with the presence of inbreeding and population decline in Iranian cattle breeds.

Genetic tests for estimating dairy breed proportion and parentage assignment in East African crossbred cattle

Strucken, Eva M.,Al-Mamun, Hawlader A.,Esquivelzeta-Rabell, Cecilia,Gondro, Cedric,Mwai, Okeyo A.,Gibson, John P. BioMed Central 2017 Genetics, selection, evolution Vol.49 No.1

<P><B>Background</B></P><P>Smallholder dairy farming in much of the developing world is based on the use of crossbred cows that combine local adaptation traits of indigenous breeds with high milk yield potential of exotic dairy breeds. Pedigree recording is rare in such systems which means that it is impossible to make informed breeding decisions. High-density single nucleotide polymorphism (SNP) assays allow accurate estimation of breed composition and parentage assignment but are too expensive for routine application. Our aim was to determine the level of accuracy achieved with low-density SNP assays.</P><P><B>Methods</B></P><P>We constructed subsets of 100 to 1500 SNPs from the 735k-SNP Illumina panel by selecting: (a) on high minor allele frequencies (MAF) in a crossbred population; (b) on large differences in allele frequency between ancestral breeds; (c) at random; or (d) with a differential evolution algorithm. These panels were tested on a dataset of 1933 crossbred dairy cattle from Kenya/Uganda and on crossbred populations from Ethiopia (N = 545) and Tanzania (N = 462). Dairy breed proportions were estimated by using the ADMIXTURE program, a regression approach, and SNP-best linear unbiased prediction, and tested against estimates obtained by ADMIXTURE based on the 735k-SNP panel. Performance for parentage assignment was based on opposing homozygotes which were used to calculate the separation value (<I>sv</I>) between true and false assignments.</P><P><B>Results</B></P><P>Panels of SNPs based on the largest differences in allele frequency between European dairy breeds and a combined Nelore/N’Dama population gave the best predictions of dairy breed proportion (r<SUP>2</SUP> = 0.962 to 0.994 for 100 to 1500 SNPs) with an average absolute bias of 0.026. Panels of SNPs based on the highest MAF in the crossbred population (Kenya/Uganda) gave the most accurate parentage assignments (<I>sv</I> = −1 to 15 for 100 to 1500 SNPs).</P><P><B>Conclusions</B></P><P>Due to the different required properties of SNPs, panels that did well for breed composition did poorly for parentage assignment and vice versa. A combined panel of 400 SNPs was not able to assign parentages correctly, thus we recommend the use of 200 SNPs either for breed proportion prediction or parentage assignment, independently.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s12711-017-0342-1) contains supplementary material, which is available to authorized users.</P>

Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes

Ferdosi, Mohammad H,Kinghorn, Brian P,van der Werf, Julius H J,Gondro, Cedric BioMed Central 2014 Genetics, selection, evolution Vol.46 No.1

<P><B>Background</B></P><P>Identifying recombination events and the chromosomal segments that constitute a gamete is useful for a number of applications in genomic analyses. In livestock, genotypic data are commonly available for half-sib families. We propose a straightforward but computationally efficient method to use single nucleotide polymorphism marker genotypes on half-sibs to reconstruct the recombination and segregation events that occurred during meiosis in a sire to form the haplotypes observed in its offspring. These meiosis events determine a block structure in paternal haplotypes of the progeny and this can be used to phase the genotypes of individuals in single half-sib families, to impute haplotypes of the sire if they are not genotyped or to impute the paternal strand of the offspring’s sequence based on sequence data of the sire.</P><P><B>Methods</B></P><P>The hsphase algorithm exploits information from opposing homozygotes among half-sibs to identify recombination events, and the chromosomal regions from the paternal and maternal strands of the sire (blocks) that were inherited by its progeny. This information is then used to impute the sire’s genotype, which, in turn, is used to phase the half-sib family. Accuracy (defined as R<SUP>2</SUP>) and performance of this approach were evaluated by using simulated and real datasets. Phasing results for the half-sibs were benchmarked to other commonly used phasing programs – AlphaPhase, BEAGLE and PedPhase 3.</P><P><B>Results</B></P><P>Using a simulated dataset with 20 markers per cM, and for a half-sib family size of 4 and 40, the accuracy of block detection, was 0.58 and 0.96, respectively. The accuracy of inferring sire genotypes was 0.75 and 1.00 and the accuracy of phasing was around 0.97, respectively. hsphase was more robust to genotyping errors than PedPhase 3, AlphaPhase and BEAGLE. Computationally, hsphase was much faster than AlphaPhase and BEAGLE.</P><P><B>Conclusions</B></P><P>In half-sib families of size 8 and above, hsphase can accurately detect block structure of paternal haplotypes, impute genotypes of ungenotyped sires and reconstruct haplotypes in progeny. The method is much faster and more accurate than other widely used population-based phasing programs. A program implementing the method is freely available as an R package (hsphase).</P>

Withdrawal: Update physical genomic information for commercial bovine SNP chip based on recent reference genome sequences (ARS-UCD1.2)

( Jeongwoen Shin ),( Dongwon Seo ),( Dong Jae Lee ),( Soohyun Lee ),( Cedric Gondro ),( Seung Hwan Lee ),( Yang-mo Koo ) 한국축산학회(구 한국동물자원과학회) 2021 한국축산학회지 Vol.63 No.3

Genome wide QTL mapping to identify candidate genes for carcass traits in Hanwoo (Korean Cattle)

이승환,Julius van der Werf,이상홍,임다정,박응우,Cedric Gondro,윤두학,오성종,김언현,John Gibson,John Thompson 한국유전학회 2012 Genes & Genomics Vol.34 No.1

Meat quality traits are the most economically important traits affecting the beef industry in Korea. We performed a whole genome quantitative trait locus (QTL) mapping study of carcass data in Hanwoo Korean cattle. Two hundred sixty-six Hanwoo steers from 65 sires were genotyped using a 10K Affymetrix SNP chip. The average SNP interval across the bovine genome was 1.5Mb. Associations between each individual SNP and four carcass traits [carcass weight (CWT),eye muscle area (EMA), back fat thickness (BFT), and marbling (MAR)] were assessed using a linear mixed model of each trait. Combined linkage and linkage disequilibrium analysis (LDLA) detected six potential QTL on BTA04, 06, 13,16, 17, and 23 at the chromosome-wise level (P<0.05). Two MAR QTL were detected at 52.2 cM of BTA06 and 46.04cM of BTA17. We identified three genes (ARAP2,LOC539460, and LOC511424) in the QTL region of BTA06and seven genes (RPS14, SCARB1, LOC782103, BRI3BP,AACS, DHX37, and UBC) in the QTL region of BTA17. One significant QTL for CWT was detected at 100 cM on BTA04and the corresponding QTL region spanned 1.7 cM from 99.7to 101.4 cM. For EMA QTL, one significant QTL was detected at 3.9 cM of BTA23 and the most likely QTL interval was 1.4 cM, placing 15 candidate genes in the marker bracket. Finally, two QTL for BFT were identified at 68 cM on BTA13and 24 cM on BTA16. The LPIN3 gene, which is functionally associated with lipodystrophy in humans, is located in the BFT QTL on BTA13. Thus, two potential candidate genes, acetoacetyl-CoA synthetase (AACS) and lipin (LPIN), were detected in QTL regions on BTA17 for MAR and BTA13 for BFT,respectively. In conclusion, LDLA analysis can be used to detect chromosome regions harboring QTL and candidate genes with a low density SNP panel, yielding relatively narrow confidence intervals regarding location.

<i>hsphase</i> : an R package for pedigree reconstruction, detection of recombination events, phasing and imputation of half-sib family groups

Ferdosi, Mohammad H,Kinghorn, Brian P,van der Werf, Julius HJ,Lee, Seung Hwan,Gondro, Cedric BioMed Central 2014 BMC bioinformatics Vol.15 No.-

<P><B>Background</B></P><P>Identification of recombination events and which chromosomal segments contributed to an individual is useful for a number of applications in genomic analyses including haplotyping, imputation, signatures of selection, and improved estimates of relationship and probability of identity by descent. Genotypic data on half-sib family groups are widely available in livestock genomics. This structure makes it possible to identify recombination events accurately even with only a few individuals and it lends itself well to a range of applications such as parentage assignment and pedigree verification.</P><P><B>Results</B></P><P>Here we present <I>hsphase</I>, an R package that exploits the genetic structure found in half-sib livestock data to identify and count recombination events, impute and phase un-genotyped sires and phase its offspring. The package also allows reconstruction of family groups (pedigree inference), identification of pedigree errors and parentage assignment. Additional functions in the package allow identification of genomic mapping errors, imputation of paternal high density genotypes from low density genotypes, evaluation of phasing results either from <I>hsphase</I> or from other phasing programs. Various diagnostic plotting functions permit rapid visual inspection of results and evaluation of datasets.</P><P><B>Conclusion</B></P><P>The <I>hsphase</I> package provides a suite of functions for analysis and visualization of genomic structures in half-sib family groups implemented in the widely used R programming environment. Low level functions were implemented in C++ and parallelized to improve performance. <I>hsphase</I> was primarily designed for use with high density SNP array data but it is fast enough to run directly on sequence data once they become more widely available. The package is available (GPL 3) from the Comprehensive R Archive Network (CRAN) or from http://www-personal.une.edu.au/~cgondro2/hsphase.htm.</P>

Analysis of extended haplotype in Korean cattle (Hanwoo) population

( Dajeong Lim ),( Bong Hwan Choi ),( Yong Min Cho ),( Han Ha Chai ),( Gul Won Jang ),( Cedric Gondro ),( Yeoung Ho Jeoung ),( Seung Hwan Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2016 BMB Reports Vol.49 No.9

Korean cattle (Hanwoo) are categorized into three breeds based on color: brown, brindle, and black. Among these breeds, brown Hanwoo has been subjected to intensive selection to improve meat traits. To identify genetic traces driven by recent selection in brown Hanwoo, we scanned the genomes of brown and brindle Hanwoo using a bovine SNP chip. We identified 17 candidate selection signatures in brown Hanwoo and sequenced four candidate regions from 10 individuals each of brown and brindle Hanwoo. In particular, non-synonymous SNPs in the ADSL gene (K88M, L189H, and R302Q) might have had mutational effects on protein structure as a result of altering the purine pathway during nucleotide breakdown. The ADSL gene was previously reported to affect meat quality and yield in livestock. Meat quality and yield are main breeding goals for brown Hanwoo, and our results support a potential causal influence of non-synonymous SNPs in the ADSL gene. [BMB Reports 2016; 49(9): 514-519]