Wan-Sheng Liu

Worldwide Patterns of Ancestry, Divergence, and Admixture in Domesticated Cattle

The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds and populations have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 animals, we evaluate the population structure of 134 domesticated bovid breeds. Regardless of the analytical method or sample subset, the three major groups of Asian indicine, Eurasian taurine, and African taurine were consistently observed. Patterns of geographic dispersal resulting from co-migration with humans and exportation are recognizable in phylogenetic networks. All analytical methods reveal patterns of hybridization which occurred after divergence. Using 19 breeds, we map the cline of indicine introgression into Africa. We infer that African taurine possess a large portion of wild African auroch ancestry, causing their divergence from Eurasian taurine. We detect exportation patterns in Asia and identify a cline of Eurasian taurine/indicine hybridization in Asia. We also identify the influence of species other than Bos taurus taurus and B. t. indicus in the formation of Asian breeds. We detect the pronounced influence of Shorthorn cattle in the formation of European breeds. Iberian and Italian cattle possess introgression from African taurine. American Criollo cattle originate from Iberia, and not directly from Africa with African ancestry inherited via Iberian ancestors. Indicine introgression into American cattle occurred in the Americas, and not Europe. We argue that cattle migration, movement and trading followed by admixture have been important forces in shaping modern bovine genomic variation.

A radiation hybrid map for the bovine Y Chromosome

Abstract. Screening a bovine Y Chromosome-specific DNA library resulted in 34 new microsatellites, six of which mapped to the pseudoautosomal region (PAR), and 28 localized to the Y-specific region. These microsatellites, together with 23 markers previously mapped to the bovine Y Chr, were scored on a 7000-rad cattle–hamster radiation hybrid (RH) panel. Retention frequency of individual markers ranged from 18.5% to 76.5% with an average of 48.4%. Markers with high retention frequency (>55%) were found to exist in multiple copies on the Y Chr. Thirteen markers were placed on the PAR RH map with the AmelY gene proximal to the pseudoautosomal boundary and 46 markers, including Sry and Tspy gene, on the Y-specific region of the RH map. The microsatellites developed and mapped in this work will be useful for comparative mapping of cattle, sheep, and goat, studying the origin, evolution, and migration of bovidae species and provide an initial platform to develop a high-resolution map of the Y Chr and positional cloning of Y-specific genes.

Short communication: Heritability of gross feed efficiency and associations with yield, intake, residual intake, body weight, and body condition score in 11 commercial Pennsylvania tie stalls

The objectives of this study were to calculate the heritability of feed efficiency and residual feed intake, and examine the relationships between feed efficiency and other traits of productive and economic importance. Intake and body measurement data were collected monthly on 970 cows in 11 tie-stall herds for 6 consecutive mo. Measures of efficiency for this study were: dry matter intake efficiency (DMIE), defined as 305-d fat-corrected milk (FCM)/305-d DMI, net energy for lactation efficiency (NELE), defined as 305-d FCM/05-d NEL intake, and crude protein efficiency (CPE), defined as 305-d true protein yield/305-d CP intake. Residual feed intake (RFI) was calculated by regressing daily DMI on daily milk, fat, and protein yields, body weight (BW), daily body condition score (BCS) gain or loss, the interaction between BW and BCS gain or loss, and days in milk (DIM). Data were analyzed with 3- and 4-trait animal models and included 305-d FCM or protein yield, DM, NEL, or CP intake, BW, BCS, BCS change between DIM 1 and 60, milk urea nitrogen, somatic cell score, RFI, or an alternative efficiency measure. Data were analyzed with and without significant covariates for BCS and BCS change between DIM 1 and 60. The average DMIE, NELE, and CPE were 1.61, 0.98, and 0.32, respectively. Heritability of gross feed efficiency was 0.14 for DMIE, 0.18 for NELE, and 0.21 for CPE, and heritability of RFI was 0.01. Body weight and BCS had high and negative correlations with the efficiency traits (-0.64 to -0.70), indicating that larger and fatter cows were less feed efficient than smaller and thinner cows. When BCS covariates were included in the model, cows identified as being highly efficient produced 2.3 kg/d less FCM in early lactation due to less early lactation loss of BCS. Results from this study suggest that selection for higher yield and lower BW will increase feed efficiency, and that body tissue mobilization should be considered.

Genetic parameters of feed intake, production, body weight, body condition score, and selected type traits of Holstein cows in commercial tie-stall barns.

The objectives of this study were to determine the feasibility of measuring feed intake in commercial tie-stall dairies and infer genetic parameters of feed intake, yield, somatic cell score, milk urea nitrogen, body weight (BW), body condition score (BCS), and linear type traits of Holstein cows. Feed intake, BW, and BCS were measured on 970 cows in 11 Pennsylvania tie-stall herds. Historical test-day data from these cows and 739 herdmates who were contemporaries during earlier lactations were also included. Feed intake was measured by researchers once per month over a 24-h period within 7 d of 6 consecutive Dairy Herd Information test days. Feed samples from each farm were collected monthly on the same day that feed intake was measured and were used to calculate intakes of dry matter, crude protein, and net energy of lactation. Test-day records were analyzed with multiple-trait animal models, and 305-d fat-corrected milk yield, dry matter intake, crude protein intake, net energy of lactation intake, average BW, and average BCS were derived from the test-day models. The 305-d traits were also analyzed with multiple-trait animal models that included a prediction of 40-wk dry matter intake derived from National Research Council equations. Heritability estimates for 305-d intake of dry matter, crude protein, and net energy of lactation ranged from 0.15 to 0.18. Genetic correlations of predicted dry matter intake with 305-d dry matter, crude protein, and net energy of lactation intake were 0.84, 0.90, and 0.94, respectively. Genetic correlations among the 3 intake traits and fat-corrected milk yield, BW, and stature were moderate to high (0.52 to 0.63). Results indicate that feed intake measured in commercial tie-stalls once per month has sufficient accuracy to enable genetic research. High-producing and larger cows were genetically inclined to have higher feed intake. The genetic correlation between observed and predicted intakes was less than unity, indicating potential variation in feed efficiency.

Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A

Summary.  Background: Large animal models that accurately mimic human hemophilia A (HA) are in great demand for developing and testing novel therapies to treat HA. Objectives: To re‐establish a line of sheep exhibiting a spontaneous bleeding disorder closely mimicking severe human HA, fully characterize their clinical presentation, and define the molecular basis for disease. Patients/methods: Sequential reproductive manipulations were performed with cryopreserved semen from a deceased affected ram. The resultant animals were examined for hematologic parameters, clinical symptoms, and responsiveness to human FVIII (hFVIII). The full coding region of sheep FVIII mRNA was sequenced to identify the genetic lesion. Results and conclusions: The combined reproductive technologies yielded 36 carriers and 8 affected animals. The latter had almost non‐existent levels of FVIII:C and extremely prolonged aPTT, with otherwise normal hematologic parameters. These animals exhibited bleeding from the umbilical cord, prolonged tail and nail cuticle bleeding time, and multiple episodes of severe spontaneous bleeding, including hemarthroses, muscle hematomas and hematuria, all of which responded to hFVIII. Inhibitors of hFVIII were detected in four treated animals, further establishing the preclinical value of this model. Sequencing identified a premature stop codon and frame‐shift in exon 14, providing a molecular explanation for HA. Given the decades of experience using sheep to study both normal physiology and a wide array of diseases and the high homology between human and sheep FVIII, this new model will enable a better understanding of HA and facilitate the development and testing of novel treatments that can directly translate to HA patients.

Male-specific region of the bovine Y chromosome is gene rich with a high transcriptomic activity in testis development

The male-specific region of the mammalian Y chromosome (MSY) contains clusters of genes essential for male reproduction. The highly repetitive and degenerative nature of the Y chromosome impedes genomic and transcriptomic characterization. Although the Y chromosome sequence is available for the human, chimpanzee, and macaque, little is known about the annotation and transcriptome of nonprimate MSY. Here, we investigated the transcriptome of the MSY in cattle by direct testis cDNA selection and RNA-seq approaches. The bovine MSY differs radically from the primate Y chromosomes with respect to its structure, gene content, and density. Among the 28 protein-coding genes/families identified on the bovine MSY (12 single- and 16 multicopy genes), 16 are bovid specific. The 1,274 genes identified in this study made the bovine MSY gene density the highest in the genome; in comparison, primate MSYs have only 31–78 genes. Our results, along with the highly transcriptional activities observed from these Y-chromosome genes and 375 additional noncoding RNAs, challenge the widely accepted hypothesis that the MSY is gene poor and transcriptionally inert. The bovine MSY genes are predominantly expressed and are differentially regulated during the testicular development. Synonymous substitution rate analyses of the multicopy MSY genes indicated that two major periods of expansion occurred during the Miocene and Pliocene, contributing to the adaptive radiation of bovids. The massive amplification and vigorous transcription suggest that the MSY serves as a genomic niche regulating male reproduction during bovid expansion.

Bovine Y chromosome microsatellite polymorphisms

Thirty-eight bovine Y chromosome (BTAY) microsatellites (MS) were assessed for polymorphisms in DNA samples obtained from 17 unrelated bulls. Thirty-three of these microsatellites are new and were used for the construction of a first generation radiation hybrid map for BTAY (Liu et al., 2002). Five MS had been previously reported and were used as positive controls. Fourteen out of 38 MS were found to be polymorphic; the remaining 24 were uninformative among the animals tested. The number of hemizygous loci per MS within individual ranged from two to over 20. Seven MS presented smear- or ladder-like bands, a unique feature for Y chromosome multi-copy hemizygous MS loci. The locus length variance, within individual, ranged from 2 to 42 bp corresponding to the MS with the minimum and maximum number of loci observed, respectively. Within the 14 polymorphic MS, the five pseudoautosomal MS, on average, were more polymorphic (35.3%) than the nine Y-specific MS (19.6%). Haplotypes resulting from combinations of these polymorphic loci will provide a powerful tool for future studies on the origin of domestic cattle and the evolution of bovid species.

MicroRNA in ovarian function

The mammalian ovary is a dynamic organ. The coordination of follicle recruitment, selection, and ovulation and the timely development and regression of the corpus luteum are essential for a functional ovary and fertility. Deregulation of any of these processes results in ovarian dysfunction and potential infertility. MicroRNA (miRNA) are short noncoding RNA that regulate developmental processes and time-sensitive functions. The expression of miRNA in the ovary varies with cell type, function, and stage of the estrous cycle. miRNA are involved in the formation of primordial follicles, follicular recruitment and selection, follicular atresia, oocyte-cumulus cell interaction, granulosal cell function, and luteinization. miRNA are differentially expressed in luteal cells at the various stages of the estrous cycle and during maternal recognition of pregnancy, suggesting a role in luteal development, maintenance, and regression. An understanding of the patterns of expression and functions of miRNA in the ovary will lead to novel therapeutics to treat ovarian dysfunction and improve fertility and, potentially, to the development of better contraceptives.

Radiation hybrid map of the porcine genome comprising 2035 EST loci

The IMpRH7000-rad radiation hybrid panel was used to map 2035 expressed sequence tags (ESTs) at a minimum LOD score of 4.0. A total of 134 linkage groups covers 57,192 cR or 78% of the predicted size of the porcine and 71% of the human genome, respectively. Approximately 81% (1649) of the porcine ESTs were annotated against the NCBI nonredundant database; 1422 mapped in silico to a location in build 35.1 of the human genome sequence (HGS) and 1185 to a gene and location in build 35.1 HGS. The map revealed 40 major breaks in synteny (1.00e−25 and lower) with the human genome, 37 of which fall within a single chromosome. At this improved level of resolution and coverage, porcine chromosomes (SSC) 2, 5, 6, 7, 12, and 14 remain “gene-rich” and homologous to human chromosomes (HSA) 17, 19, and 22, while SSC 1, 8, 11, and X have been confirmed to correspond to the “gene-deserts” on HSA 18, 4, 13, and X.

The expansion of the PRAME gene family in Eutheria.

The PRAME gene family belongs to the group of cancer/testis genes whose expression is restricted primarily to the testis and a variety of cancers. The expansion of this gene family as a result of gene duplication has been observed in primates and rodents. We analyzed the PRAME gene family in Eutheria and discovered a novel Y-linked PRAME gene family in bovine, PRAMEY, which underwent amplification after a lineage-specific, autosome-to-Y transposition. Phylogenetic analyses revealed two major evolutionary clades. Clade I containing the amplified PRAMEYs and the unamplified autosomal homologs in cattle and other eutherians is under stronger functional constraints; whereas, Clade II containing the amplified autosomal PRAMEs is under positive selection. Deep-sequencing analysis indicated that eight of the identified 16 PRAMEY loci are active transcriptionally. Compared to the bovine autosomal PRAME that is expressed predominantly in testis, the PRAMEY gene family is expressed exclusively in testis and is up-regulated during testicular maturation. Furthermore, the sense RNA of PRAMEY is expressed specifically whereas the antisense RNA is expressed predominantly in spermatids. This study revealed that the expansion of the PRAME family occurred in both autosomes and sex chromosomes in a lineage-dependent manner. Differential selection forces have shaped the evolution and function of the PRAME family. The positive selection observed on the autosomal PRAMEs (Clade II) may result in their functional diversification in immunity and reproduction. Conversely, selective constraints have operated on the expanded PRAMEYs to preserve their essential function in spermatogenesis.