Cattle Chromosomes Research Articles

PSVIII-21 Bivariate genomic prediction with different heritability, QTL and SNP panel scenarios using artificial neural network

Abstract A bivariate simulation study was carried out to compare the accuracies of genomic predictions from bivariate artificial neural network model with 1 to 10 neurons (ANN-1–10) using the SNPs on the first chromosome of Brangus beef cattle for 50% genetically correlated two traits with heritabilities of 25% and 50% (T1h2=0.25 and T2h2=0.5) determined either by 50, 100, 250 or 500 QTL. After QTL were created by randomly selecting 50, 100, 250 and 500 SNPs from the 3361 SNPs of 719 animals, their effects were sampled from a bivariate normal distribution. The breeding value of animal i in each QTL scenario was generated as Σgijβ j where gij is the genotype of animal i at QTL j and the vector of β j has the effects of QTL j from a bivariate normal distribution for T1h2=0.25 and T2h2=0.5. Phenotypic values (Σgijβ j+ei) of animal i for traits were generated by adding residuals (ei) from a bivariate normal distribution to the Σgijβ j of animal i. Genomic predictions for T1h2=0.25 and T2h2=0.5 were carried out by bivariate Feed Forward MultiLayer Perceptron ANN-1–10 neurons with three sets of SNP panels, only QTL genotypes (Panel1), all SNP markers, including the QTL (Panel2), and all SNP markers, excluding the QTL (Panel3). The correlations between phenotypes and predicted phenotypes from 10-fold cross validation for bivariate analysis of T1h2=0.25 and T2h2=0.5 were used to assess predictive ability of bivariate ANN-1–10 neurons based on 4 QTL scenarios with 3 Panels of SNP panels. Correlations for genomic predictions of T2h2=0.5 were higher than those from T2h2=0.25 for all QTL and Panel scenarios (Table 1). Panle2 including QTL and SNP performs better prediction than Panel1 and Panel3 in QTL100, QTL250 and QTL500 scenarios and the correlation from Panel3 including only SNP, which is more realistic, are similar to or higher than those from Panel1.

New insights into mammalian sex chromosome structure and evolution using high-quality sequences from bovine X and Y chromosomes

BackgroundMammalian X chromosomes are mainly euchromatic with a similar size and structure among species whereas Y chromosomes are smaller, have undergone substantial evolutionary changes and accumulated male specific genes and genes involved in sex determination. The pseudoautosomal region (PAR) is conserved on the X and Y and pair during meiosis. The structure, evolution and function of mammalian sex chromosomes, particularly the Y chromsome, is still poorly understood because few species have high quality sex chromosome assemblies.ResultsHere we report the first bovine sex chromosome assemblies that include the complete PAR spanning 6.84 Mb and three Y chromosome X-degenerate (X-d) regions. The PAR comprises 31 genes, including genes that are missing from the X chromosome in current cattle, sheep and goat reference genomes. Twenty-nine PAR genes are single-copy genes and two are multi-copy gene families, OBP, which has 3 copies and BDA20, which has 4 copies. The Y chromosome X-d1, 2a and 2b regions contain 11, 2 and 2 gametologs, respectively.ConclusionsThe ruminant PAR comprises 31 genes and is similar to the PAR of pig and dog but extends further than those of human and horse. Differences in the pseudoautosomal boundaries are consistent with evolutionary divergence times. A bovidae-specific expansion of members of the lipocalin gene family in the PAR reported here, may affect immune-modulation and anti-inflammatory responses in ruminants. Comparison of the X-d regions of Y chromosomes across species revealed that five of the X-Y gametologs, which are known to be global regulators of gene activity and candidate sexual dimorphism genes, are conserved.

An integrated chromosome-scale genome assembly of the Masai giraffe (Giraffa camelopardalis tippelskirchi).

BackgroundThe Masai giraffe (Giraffa camelopardalis tippelskirchi) is the largest-bodied giraffe and the world's tallest terrestrial animal. With its extreme size and height, the giraffe's unique anatomical and physiological adaptations have long been of interest to diverse research fields. Giraffes are also critical to ecosystems of sub-Saharan Africa, with their long neck serving as a conduit to food sources not shared by other herbivores. Although the genome of a Masai giraffe has been sequenced, the assembly was highly fragmented and suboptimal for genome analysis. Herein we report an improved giraffe genome assembly to facilitate evolutionary analysis of the giraffe and other ruminant genomes.FindingsUsing SOAPdenovo2 and 170 Gbp of Illumina paired-end and mate-pair reads, we generated a 2.6-Gbp male Masai giraffe genome assembly, with a scaffold N50 of 3 Mbp. The incorporation of 114.6 Gbp of Chicago library sequencing data resulted in a HiRise SOAPdenovo + Chicago assembly with an N50 of 48 Mbp and containing 95% of expected genes according to BUSCO analysis. Using the Reference-Assisted Chromosome Assembly tool, we were able to order and orient scaffolds into 42 predicted chromosome fragments (PCFs). Using fluorescence in situ hybridization, we placed 153 cattle bacterial artificial chromosomes onto giraffe metaphase spreads to assess and assign the PCFs on 14 giraffe autosomes and the X chromosome resulting in the final assembly with an N50 of 177.94 Mbp. In this assembly, 21,621 protein-coding genes were identified using both de novo and homology-based predictions.ConclusionsWe have produced the first chromosome-scale genome assembly for a Giraffidae species. This assembly provides a valuable resource for the study of artiodactyl evolution and for understanding the molecular basis of the unique adaptive traits of giraffes. In addition, the assembly will provide a powerful resource to assist conservation efforts of Masai giraffe, whose population size has declined by 52% in recent years.

The first chromosome-level genome for a marine mammal as a resource to study ecology and evolution.

Marine mammals are important models for studying convergent evolution and aquatic adaption, and thus reference genomes of marine mammals can provide evolutionary insights. Here, we present the first chromosome-level marine mammal genome assembly based on the data generated by the BGISEQ-500 platform, for a stranded female sperm whale (Physeter macrocephalus). Using this reference genome, we performed chromosome evolution analysis of the sperm whale, including constructing ancestral chromosomes, identifying chromosome rearrangement events and comparing with cattle chromosomes, which provides a resource for exploring marine mammal adaptation and speciation. We detected a high proportion of long interspersed nuclear elements and expanded gene families, and contraction of major histocompatibility complex region genes which were specific to sperm whale. Using comparisons with sheep and cattle, we analysed positively selected genes to identify gene pathways that may be related to adaptation to the marine environment. Further, we identified possible convergent evolution in aquatic mammals by testing for positively selected genes across three orders of marine mammals. In addition, we used publicly available resequencing data to confirm a rapid decline in global population size in the Pliocene to Pleistocene transition. This study sheds light on the chromosome evolution and genetic mechanisms underpinning sperm whale adaptations, providing valuable resources for future comparative genomics.

Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression

BackgroundAn unfavorable genetic correlation between milk production and fertility makes simultaneous improvement of milk production and fertility difficult in cattle breeding. Rapid genetic improvement in milk production traits in dairy cattle has been accompanied by decline in cow fertility. The genetic basis of this correlation remains poorly understood. Expanded reference populations and large sets of sequenced animals make genome-wide association studies (GWAS) with imputed markers possible for large populations and thereby studying genetic architecture of complex traits.ResultsIn this study, we associated 15,551,021 SNPs with female fertility index in 5038 Nordic Holstein cattle. We have identified seven quantitative trait loci (QTL) on six chromosomes in cattle. Along with nearest genes to GWAS hits, we used gene-based analysis and spread of linkage disequilibrium (LD) information to generate a list of potential candidate genes affecting fertility in cattle. Subsequently, we used prior knowledge on gene related to fertility from Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathway analysis, mammalian phenotype database, and public available RNA-seq data to refine the list of candidate genes for fertility. We used variant annotations to investigate candidate mutations within the prioritized candidate genes. Using multiple source of information, we proposed candidate genes with biological relevance underlying each of these seven QTL. On chromosome 1, we have identified ten candidate genes for two QTL. For the rest of chromosomes, we proposed one candidate gene for each QTL. In the candidate genes list, differentially expressed genes from different studies support FRAS1, ITGB5, ADCY5, and SEMA5B as candidate genes for cow fertility.ConclusionThe GWAS result not only confirmed previously mapped QTL, but also made new findings. Our findings contributes towards dissecting the genetics for female fertility in cattle. Moreover, this study shows the usefulness of adding independent information to pick candidate genes during post-GWAS analysis.

Genome-wide association study and scan for signatures of selection point to candidate genes for body temperature maintenance under the cold stress in Siberian cattle populations

BackgroundDesign of new highly productive livestock breeds, well-adapted to local climatic conditions is one of the aims of modern agriculture and breeding. The genetics underlying economically important traits in cattle are widely studied, whereas our knowledge of the genetic mechanisms of adaptation to local environments is still scarce. To address this issue for cold climates we used an integrated approach for detecting genomic intervals related to body temperature maintenance under acute cold stress. Our approach combined genome-wide association studies (GWAS) and scans for signatures of selection applied to a cattle population (Hereford and Kazakh Whiteheaded beef breeds) bred in Siberia. We utilized the GGP HD150K DNA chip containing 139,376 single nucleotide polymorphism markers.ResultsWe detected a single candidate region on cattle chromosome (BTA)15 overlapping between the GWAS results and the results of scans for selective sweeps. This region contains two genes, MSANTD4 and GRIA4. Both genes are functional candidates to contribute to the cold-stress resistance phenotype, due to their indirect involvement in the cold shock response (MSANTD4) and body thermoregulation (GRIA4).ConclusionsOur results point to a novel region on BTA15 which is a candidate region associated with the body temperature maintenance phenotype in Siberian cattle. The results of our research and the follow up studies might be used for the development of cattle breeds better adapted to cold climates of the Russian Federation and other Northern countries with similar climates.

In silico identification of conserved miRNAs and their selective target gene prediction in indicine (Bos indicus) cattle.

The modern cattle was domesticated from aurochs, sharing its physiological traits into two subspecies Bos taurus and Bos indicus. MicroRNAs (miRNAs) are a class of non-coding short RNAs of ~22nt which have a key role in the regulation of many cellular and physiological processes in the animal. The current study was aimed to predict and annotate the potential mutations in indicine miRNAs throughout the genome using de novo and homology-based in silico approaches. Genome-wide mapping was performed in available indicine assembly by the homology-based approach and 768 miRNAs were recovered out of 808 reported taurine miRNAs belonging to 521 unique mature miRNA families. While 42 precursors were dropped due to lack of secondary miRNA structure, increasing stringency or decreasing similarity between the two genomes’ miRNA. Increasing tendency of miRNAs incidence was observed on chr5, chr7, chr8, chr12 and chr21 with 19 polycistronic miRNA within 1-kilobase distance throughout the indicine genome. Notably, 12 miRNAs showed copy number variation. Eighteen miRNAs showed a mutation in their mature sequences in which eight were found in their seed region. Whilst in de novo based approach, 12 novel potential miRNAs on Y chromosome in indicine cattle along with a new miRNA (bind-miR-1264) on chrX were found. The final data set is annotated and explains the impending target genes that are responsible for enhanced immunity, heat tolerance and disease tolerance regulation in indicine. The study conforms to better understanding and perceptive approach towards indicine genome.

Genes related to the white face colour pattern in eight Russian cattle breeds

One of the major effects of domestication is change of animal coat colour to up to complete white colour of the whole body. It is possible that white colour of livestock animals had aesthetic significance for humans as well. The first step towards detection of genes and mutations controlling white colouring in animals is the genome-wide association studies. These studies, however, have not been done for the cattle breeds native to the Russian Federation. The aim of this study was therefore to identify genomic intervals and candidate genes that could be responsible for white face colouring in eight Russian cattle breeds. The data on genome-wide genotyping of 131,709 high-quality single nucleotide polymorphisms (SNPs) on 148 animas have been used in the program ­EMMAX. Association analysis has been performed using two related phenotypes: a) the white face with the rest of the body of any colour and b) white face with the rest of the body of different (non-white) colour. In the first case, the only statistically significant marker found was the SNP BovineHD0500019319 located on cattle chromosome (BTA) 5. The same SNP was the most significant within the cluster of three SNPs on BTA5: 68,803,879–69,365,854 associated also with the second phenotype. Five genes were found within this interval in the cattle genome, out of which the most likely functional candidate was SLC41A2, with the SNP BovineHD0500019319 found within its intronic sequence. SLC41A2 encodes a magnesium transporter protein. However, the function of this gene is not well established. Other members of this gene family are the key genes controlling differences in human skin and animal coat colour. Additional significant association signals with the second phenotype have been detected in BTA 1–4, 6–15, 18, 19, 24, 27, and 29. Overall, 37 genomic intervals have been detected associated with white face colouring in eight Russian native cattle breeds.

Genetic variation and gene conversions within the bovine NK-lysin gene family.

In contrast to a single copy of the NK-lysin gene in humans and many other mammals, we previously identified a family of four expressed NK-lysin genes arising by tandem duplications on cattle chromosome 11. Here, we report two genetic variants in the bovine NK-lysin complex with potential importance in the bovine innate immune system. The first one is a 9-bp deletion causing a three-amino-acid deletion in the pro-region of the NK1 gene product. The second is a deletion of NK2B in some Holstein cattle, resulting in copy number variation that is in disequilibrium with a SNP from the bovine 770K HD SNP array. We also show evidence for gene conversions within the three new NK2 genes, which at least partially accounts for their high degree of sequence identity.

Three intronic lncRNAs with monoallelic expression derived from the MEG8 gene in cattle.

The field of long noncoding RNA (lncRNA) research has been rapidly advancing in recent years. Antisense lncRNAs, intergenetic lncRNAs and enhancer lncRNAs can regulate genomic imprinting, which leads to parent-origin-specific monoalletic expression of genes. However, the function of intronic ncRNAs in genomic imprinting remains unclear. Previously, we obtained the cDNA sequence of cattle MEG8 gene, which is located in the DLK1-DIO3 imprinted clusters of cattle chromosome 21. In this study, we undertook a systematic search for transcripts mapping to the MEG8 intronic region and identified three novel lncRNAs, named MEG8 intronic RNA 1 (MEG8-IT1), MEG8 intronic RNA 2 (MEG8-IT2) and MEG8 intronic RNA 3 (MEG8-IT3) according to the GENCODE annotated bibliography. We characterized the expression pattern of these lncRNAs using RT-PCR in adult cattle tissues, and they were expressed in all tested eight tissues, similar to the expression pattern of MEG8. The allele-specific expression of three novel lncRNAs was assessed using a polymorphism-based sequencing approach. Three single nucleotide polymorphism sites were identified in these three lncRNAs. We found that the three lncRNAs showed monoallelic expression in the analyzed tissues, suggesting that they may be imprinted in cattle. These results expand the number of known monoallelically expressed lncRNAs from the DLK1-DIO3 domain and contribute to further investigation of lncRNA regulatory mechanisms and function.

An imprinted long noncoding RNA located between genes Meg8 and Meg9 in the cattle Dlk1-Dio3 domain.

The Dlk1-Dio3 imprinted domain is located on the cattle chromosome 21 and contains three paternally expressed protein-coding genes and a number of maternally expressed short or long noncoding RNA genes. We have previously obtained two maternally expressed long noncoding RNA genes, Meg8 and Meg9, from the cattle. In this study, we identified a novel noncoding RNA located between Meg8 and Meg9 known as LINC24061 according to the GENCODE annotated bibliography. Two alternatively spliced transcripts (LINC24061-v1 and LINC24061-v2) were obtained using RT-PCR and RACE, and the expression pattern of LINC24061-v1 and LINC24061-v2 was shown to be tissue-specific. The LINC24061-v1 splice variant was expressed in only three types of tissues: heart, kidney and muscle; in contrast, LINC24061-v2 was expressed in all eight tissues examined, including heart, liver, spleen, lung, kidney, skeletal muscle, subcutaneous fat, and brain of adult cattle. The allele-specific expression of LINC24061 was identified based on a single nucleotide polymorphism (SNP) in exon 2 of LINC24061. The results showed that LINC24061 exhibited monoallelic expression in all the examined cattle tissues.

Short communication: Imputation of markers on the bovine X chromosome

Imputation is a cost-effective approach to augment marker data for genomic selection and genome-wide association studies. However, most imputation studies have focused on autosomes. Here, we assessed the imputation of markers on the X chromosome in Holstein cattle for nongenotyped animals and animals genotyped with low-density (Illumina BovineLD, Illumina Inc., San Diego, CA) chips, using animals genotyped with medium-density (Illumina BovineSNP50) chips. A total of 26,884 genotyped Holstein individuals genotyped with medium-density chips were used in this study. Imputation was carried out using FImpute V2.2. The following parameters were examined: treating the pseudoautosomal region as autosomal or as X specific, different sizes of reference groups, different male/female proportions in the reference group, and cumulated degree of relationship between the reference group and target group. The imputation accuracy of markers on the X chromosome was improved if the pseudoautosomal region was treated as autosomal. Increasing the proportion of females in the reference group improved the imputation accuracy for the X chromosome. Imputation for nongenotyped animals in general had lower accuracy compared with animals genotyped with the low-density single nucleotide polymorphism array. In addition, higher cumulative pedigree relationships between the reference group and the target animal led to higher imputation accuracy. In the future, better marker coverage of the X chromosome should be developed to facilitate genomic studies involving the X chromosome.

Characterization of Korean Native Cattle Breeds by Microsatellite Markers on Sex Chromosomes

This study aimed to identify allele variability and determine the frequencies of microsatellite (MS) markers specific to bovine sex chromosomes in Korean native cattle (KNC; Chikso, Hanwoo and Jeju Black). The three KNC breeds were characterized using 4 MS markers (INRA30, TGLA325, UMN0905 and UMN0929), and allelic richness, allele frequency, heterozygosity and polymorphism information content (PIC) per locus were calculated. The mean observed heterozygosity and PIC values for Chikso, Jeju Black and Hanwoo were 0.541 and 0.542, 0.406 and 0.377, and 0.61 and 0.6, respectively. The heterozygosity and the PIC values of Jeju Black breed were smaller than those of Chikso and Hanwoo. Thus, these genetic parameters were used for the characterization of the breeds and for determining their genetic relationships. The findings of this study might be useful for the conservation, management, and utilization of KNC breeds as genetic resources.

Bovine NK-lysin: Copy number variation and functional diversification

NK-lysin is an antimicrobial peptide and effector protein in the host innate immune system. It is coded by a single gene in humans and most other mammalian species. In this study, we provide evidence for the existence of four NK-lysin genes in a repetitive region on cattle chromosome 11. The NK2A, NK2B, and NK2C genes are tandemly arrayed as three copies in ∼30-35-kb segments, located 41.8 kb upstream of NK1. All four genes are functional, albeit with differential tissue expression. NK1, NK2A, and NK2B exhibited the highest expression in intestine Peyer's patch, whereas NK2C was expressed almost exclusively in lung. The four peptide products were synthesized ex vivo, and their antimicrobial effects against both Gram-positive and Gram-negative bacteria were confirmed with a bacteria-killing assay. Transmission electron microcopy indicated that bovine NK-lysins exhibited their antimicrobial activities by lytic action in the cell membranes. In summary, the single NK-lysin gene in other mammals has expanded to a four-member gene family by tandem duplications in cattle; all four genes are transcribed, and the synthetic peptides corresponding to the core regions are biologically active and likely contribute to innate immunity in ruminants.

Variation of Meiotic Recombination Rates and MLH1 Foci Distribution in Spermatocytes of Cattle, Sheep and Goats

Despite similar genome sizes, a great variability in recombination rates is observed in mammals. We used antibodies against SYCP3, MLH1 and centromeres to compare crossover frequency, position along chromosome arms and the effect of crossover interference in spermatocytes of 4 species from the family Bovidae (Bos taurus, 2n = 60, tribe Bovini; Ovis aries, 2n = 54, Capra hircus, 2n = 60 and Ammotragus lervia, 2n = 58, tribe Caprini). Despite significant individual variability, our results also show significant differences in both recombination rates and the total length of autosomal synaptonemal complexes (SC) between cattle (47.53 MLH1 foci/cell, 244.59 µm) and members of the tribe Caprini (61.83 MLH1 foci, 296.19 µm) which can be explained by the length of time that has passed since their evolutionary divergence. Sheep displayed the highest number of MLH1 foci per cell and recombination density, although they have a lower diploid chromosome number caused by centric fusions corresponding to cattle chromosomes 1;3, 2;8 and 5;11. However, the proportion of MLH1 foci observed on the fused chromosomes in sheep (26.14%) was significantly lower than on the orthologous acrocentrics in cattle (27.6%) and goats (28.2%), and their distribution along the SC arms differed significantly. The reduced recombination rate in metacentrics is probably caused by interference acting across the centromere.

Expansion of the HSFY gene family in pig lineages : HSFY expansion in suids.

BackgroundAmplified gene families on sex chromosomes can harbour genes with important biological functions, especially relating to fertility. The Y-linked heat shock transcription factor (HSFY) family has become amplified on the Y chromosome of the domestic pig (Sus scrofa), in an apparently independent event to an HSFY expansion on the Y chromosome of cattle (Bos taurus). Although the biological functions of HSFY genes are poorly understood, they appear to be involved in gametogenesis in a number of mammalian species, and, in cattle, HSFY gene copy number may correlate with levels of fertility.ResultsWe have investigated the HSFY family in domestic pig, and other suid species including warthog, bushpig, babirusa and peccaries. The domestic pig contains at least two amplified variants of HSFY, distinguished predominantly by presence or absence of a SINE within the intron. Both these variants are expressed in testis, and both are present in approximately 50 copies each in a single cluster on the short arm of the Y. The longer form has multiple nonsense mutations rendering it likely non-functional, but many of the shorter forms still have coding potential. Other suid species also have these two variants of HSFY, and estimates of copy number suggest the HSFY family may have amplified independently twice during suid evolution.ConclusionsThe HSFY genes have become amplified in multiple species lineages independently. HSFY is predominantly expressed in testis in domestic pig, a pattern conserved with cattle, in which HSFY may play a role in fertility. Further investigation of the potential associations of HSFY with fertility and testis development may be of agricultural interest.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1650-x) contains supplementary material, which is available to authorized users.

Polymorphisms within the APOBR gene are highly associated with milk levels of prognostic ketosis biomarkers in dairy cows.

Essentially all high-yielding dairy cows experience a negative energy balance during early lactation leading to increased lipomobilization, which is a normal physiological response. However, a severe energy deficit may lead to high levels of ketone bodies and, subsequently, to subclinical or clinical ketosis. It has previously been reported that the ratio of glycerophosphocholine to phosphocholine in milk is a prognostic biomarker for the risk of ketosis in dairy cattle. It was hypothesized that this ratio reflects the ability to break down blood phosphatidylcholine as a fatty acid resource. In the current study, 248 animals from a previous study were genotyped with Illumina BovineSNP50 BeadChip, and genome-wide association studies were carried out for the milk levels of phosphocholine, glycerophosphocholine, and the ratio of both metabolites. It was demonstrated that the latter two traits are heritable with h2 = 0.43 and h2 = 0.34, respectively. A major quantitative trait locus was identified on cattle chromosome 25. The APOBR gene, coding for the apolipoprotein B receptor, is located within this region and was analyzed as a candidate gene. The analysis revealed highly significant associations of polymorphisms within the gene with glycerophosphocholine as well as the metabolite ratio. These findings support the hypothesis that differences in the ability to take up blood phosphatidylcholine from low-density lipoproteins play an important role in early lactation metabolic stability of dairy cows and indicate APOBR to contain a causative variant.

Low frequency of Y anomaly detected in Australian Brahman cow-herds

Indicine cattle have lower reproductive performance in comparison to taurine. A chromosomal anomaly characterized by the presence Y markers in females was reported and associated with infertility in cattle. The aim of this study was to investigate the occurrence of the anomaly in Brahman cows. Brahman cows (n=929) were genotyped for a Y chromosome specific region using real time-PCR. Only six out of 929 cows had the anomaly (0.6%). The anomaly frequency was much lower in Brahman cows than in the crossbred population, in which it was first detected. It also seems that the anomaly doesn't affect pregnancy in the population. Due to the low frequency, association analyses couldn't be executed. Further, SNP signal of the pseudoautosomal boundary region of the Y chromosome was investigated using HD SNP chip. Pooled DNA of “non-pregnant” and “pregnant” cows were compared and no difference in SNP allele frequency was observed. Results suggest that the anomaly had a very low frequency in this Australian Brahman population and had no effect on reproduction. Further studies comparing pregnant cows and cows that failed to conceive should be executed after better assembly and annotation of the Y chromosome in cattle.

New cryptic karyotypic differences between cattle (Bos taurus) and goat (Capra hircus).

Cattle (Bos taurus) and goat (Capra hircus) belong to the Bovidae family, and they share a common ancestor 19.7-21.5Ma ago (MYA). The Bovidae family apparently experienced a rapid species radiation in the middle Miocene. The present day cattle and goat possess the same diploid chromosome number (2n = 60) and structurally similar autosomes, except that a small subcentromeric portion of cattle chromosome nine has been translocated to goat chromosome 14. In this study, we adopted a new strategy that involves the use of bioinformatics approach to detect unknown cryptic chromosome divergences between cattle and goat using and subsequent validation using the fluorescence in situ hybridization (FISH) of bacterial artificial chromosome clones. We identified two hypothetical discrepancies between the cattle and goat genome assemblies: an inversion in the goat chromosome 13 and a transposition in the goat chromosome 6. The FISH technique allowed clear validation of the existence of a new 7.4Mb chromosomal inversion in the goat chromosome 13. Regarding the transposition in the goat chromosome six, FISH analyses revealed that the cattle and goat genomes shared the same organization, with the assembly of the goat genome being the correct one. Moreover, we defined, for the first time, the size and orientation of the translocated fragment involved in the evolutionary translocation between cattle chromosomes 9 and goat chromosome 14. Our results suggest that bioinformatics represents an efficient method for detecting cryptic chromosome divergences among species.

Looking the cow in the eye: deletion in the NID1 gene is associated with recessive inherited cataract in Romagnola cattle.

Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.