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Biomedical subjects

J E Beever

Publications and source records attributed to J E Beever.

At least 19 recordsLinked to original sources
PubMed2006

A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep.

Ovine hereditary chondrodysplasia, or spider lamb syndrome (SLS), is a genetic disorder that is characterized by severe skeletal abnormalities and has resulted in substantial economic losses for sheep producers. Here we demonstrate that a non-synonymous T>A transversion in the highly conserved tyrosine kinase II domain of a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3), is responsible for SLS. We also demonstrate that the mutant FGFR3 allele has an additive effect on long-bone length, calling into question the long-standing belief that SLS is inherited as a strict monogenic, Mendelian recessive trait. Instead, we suggest that SLS manifestation is determined primarily by the presence of the mutant FGFR3 allele, but it is also influenced by an animal's genetic background. In contrast to FGFR3 mutations causing dwarfism in humans, this single-base change is the only known natural mutation of FGFR3 that results in a skeletal overgrowth phenotype in any species.

Amino Acid Sequence↗
PubMed2005

Evaluation of approaches to detect quantitative trait loci for growth, carcass, and meat quality on swine chromosomes 2, 6, 13, and 18. II. Multivariate and principal component analyses.

The merits of complementary multivariate techniques to identify QTL associated with multiple traits were evaluated. Records from 806 F2 pigs pertaining to a Berkshire x Duroc three-generation population were available. Six multitrait groups on SSC 2, 6, 13, and 18 with information on 30 markers were studied. Multivariate techniques studied included multivariate models and principal components analysis of each multitrait group. All models included, in addition to systematic effects, additive, dominance, and imprinting coefficients corresponding to a one-QTL model and a random family effect. Multivariate analysis identified QTL associated with genomewise significant variation in four of the multitrait groups. The majority of the multivariate analysis provided greater precision of parameter estimates and higher statistical significance in some cases than univariate approaches, because of the greater parameterization of the multivariate models and moderate information content of the data. Principal component analysis results were consistent with univariate and multivariate analyses and recovered the levels of statistical significance observed in univariate analyses on the original data. In addition, principal component analysis was able to provide a location associated with LM area not detected by other analyses. The relative advantage of multivariate over the univariate approaches varied with the level of genetic covariance between traits because of the modeled QTL effect and information contained in the data; however, multivariate approaches have the unique capability to identify pleiotropic effects or multiple linked QTL.

Animals↗
PubMed2005

Evaluation of approaches to detect quantitative trait loci for growth, carcass, and meat quality on swine chromosomes 2, 6, 13, and 18. I. Univariate outbred F2 and sib-pair analyses.

Results from univariate outbred F2 interval mapping and sib-pair analyses of 12 growth and 28 carcass traits to identify QTL on SSC 2, 6, 13, and 18 were compared. Phenotypic and genetic data were recorded on a three-generation resource population including 832 F2 pigs from a cross between three Berkshire sires and 18 Duroc dams. Thirty markers with an average spacing of approximately 16 cM were genotyped across the four chromosomes. The outbred F2 mixed model included the effects of sex, birth month, and year, one-QTL additive, dominance and imprinting coefficients calculated every 1 cM using interval mapping, and a random family effect. The general sib-pair model used to describe the phenotypic differences between sib-pairs included the same systematic and random effects and a one-QTL additive coefficient calculated every 1 cM. The outbred F2 analysis found significant evidence of QTL on SSC 2 associated with 105-d weight, backfat thicknesses, LM area, fat percent, shear force, juiciness, marbling, and tenderness. In addition, QTL were identified on SSC 6 relating to 42-d weight and LM area, and on SSC 18 for fat and moisture percents. In most instances, the outbred F2 approach offered greater power to detect QTL; however, the sib-pair analysis offered greater power in several instances. The trait-specific superiority could be due to the relative advantage of each model within a trait data set. The two approaches provided complementary evidence for QTL segregating between the Berkshire and Duroc breeds used in the study that may be used to aid marker-assisted introgression and selection and candidate gene studies to improve swine growth and meat quality characteristics.

Animals↗
PubMed2004

Identification of a mutation associated with factor XI deficiency in Holstein cattle.

An autosomal recessive deficiency of blood coagulation factor XI (FXI) has been described in Holstein cattle. Current testing methods are unsuitable for accurately identifying carriers (heterozygotes) of the disease. To identify the molecular basis of this deficiency, a polymerase chain reaction (PCR)-based strategy was implemented to clone and sequence the bovine FXI gene (F11) from animals of different genotypes. Approximately 14 kb of genomic DNA sequence and 1.8 kb of cDNA sequence, corresponding to exon 3 through the 3'-UTR, of the bovine gene were obtained. Comparison of sequences derived from homozygous normal and deficient individuals revealed that FXI deficiency in Holsteins is associated with the insertion of a 76 bp segment [AT(A)(28)TAAAG(A)(26)GGAAATAATAATTCA] within exon 12. This insertion introduces a stop codon that results in a mature FXI protein lacking the functional protease domain encoded by exons 13, 14 and 15. Based on these data, a DNA-based diagnostic test has been developed for accurate genotyping. Using this method, the frequency of the mutated allele has been determined to be 1.2% in a contemporary population of the USA Holstein sires.

Animals↗
PubMed2001

Fine-mapping and construction of a bovine contig spanning the ovine callipyge locus.

The callipyge (CLPG) gene was fine-mapped by linkage analysis to a 4.6-cM chromosome interval on distal ovine OAR18q, flanked by microsatellite markers IDVGA30 and OY3. The OAR18q linkage map and human HSA14q transcript map were aligned by genotyping two bovine-hamster whole-genome radiation hybrid panels with the microsatellite markers, as well as with sequences corresponding to HSA 14q genes. Using Type I loci mapping to the IDVGA30-OY3 interval as anchor points, we have constructed a 1.4-Mb bovine BAC contig containing the IDVGA30-OY3 interval. We demonstrate that the IDVGA30-OY3 interval spans approximately 770 kb and contains at least four genes: YY1, WARS, DLK1, and GTL2.

Animals↗
PubMed2001

Development and mapping of microsatellites from a microdissected BTA 11-specific DNA library.

A chromosome-specific library was developed for Bos taurus autosome 11 by chromosome microdissection and microcloning using a bovine primary fibroblast culture, obtained from a t(X;23) heifer, that spontaneously developed a translocation chromosome involving bovine chromosome 11. The library was screened using (AC)12 oligos, positive clones selected, sequenced and primers developed to generate bovine chromosome 11-specific microsatellite markers. This study suggests that chromosome-specific libraries have great potential for development of microsatellite markers for the construction of marker-saturated linkage maps for each chromosome.

Animals↗
PubMed2001

Differential expression of the GTL2 gene within the callipyge region of ovine chromosome 18.

The inheritance pattern of the skeletal muscle hypertrophy phenotype caused by the callipyge gene has been characterized as polar overdominance. We hypothesized that this trait may be caused by a gain or loss of gene expression because of the reversible nature of the phenotype in paternal vs. maternal inheritance. Suppression subtraction cDNA probes were made from skeletal muscle mRNA of normal (NN) and callipyge (C(Pat)N(Mat)) animals and hybridized to Southern blots containing bacterial artificial chromosomes (BACs) that comprise a physical contig of the callipyge region. The CN-NN probes hybridized to two ovine and seven bovine BACs. Sequence analysis of fragments within those BACs indicated short regions of similarity to mouse gene trap locus (gtl2). Northern blots analysis of RNA from hypertrophy-responsive muscles show a population of GTL2 mRNA centred around 2.4 kb that were abundantly expressed in 14-day prenatal NN and C(Pat)N(Mat) lambs but were down-regulated in day 14 and day 56 postnatal NN lambs. The expression of GTL2 remained elevated in 14- and 56-day-old C(Pat)N(Mat) lambs as well as in 56-day-old N(Pat)C(Mat) and CC lambs. Expression of GTL2 in the supraspinatus, which does not undergo hypertrophy, was very low for all genotypes and ages. Isolation of cDNA sequences show extensive alternative splicing and a lack of codon bias suggesting that GTL2 does not encode a protein. The mutation of the callipyge allele has altered postnatal expression of GTL2 in muscles that undergo hypertrophy and will help identify mechanisms involved in growth, genomic imprinting and polar overdominance.

Alternative Splicing↗
PubMed2000

Phylogenomic analysis of the alpha proteasome gene family from early-diverging eukaryotes.

We employed a phylogenomic approach to study the evolution of alpha subunits of the proteasome gene family from early diverging eukaryotes. BLAST similarity searches of the Giardia lamblia genome identified all seven alpha proteasome genes characteristic of eukaryotes from the crown group. In addition, a PCR strategy for the amplification of multiple alpha subunit sequences generated single alpha proteasome products for representatives of the Kinetoplastida (Leishmania major), the Parabasalia (Trichomonas vaginalis), and the Microsporidia (Vairimorpha sp., Nosema sp., Endoreticulata sp., and Spraguea lophii). The kinetoplastid Trypanosoma cruzi and the eukaryote crown group Acanthamoeba castellanii yielded two distinct alpha proteasome genes each. The presence of seven distinct alpha proteasome genes in G. lamblia, one of the earliest-diverging eukaryotes, indicates that the alpha proteasome gene family evolved rapidly from a minimum of one gene in Archaea to seven or more in Eukarya. Results from the phylogenomic analysis are consistent with the idea that the Diplomonida (as represented by G. lamblia), the Kinetoplastida, the Parabasalia, and the Microsporidia diverged after the duplication events that originated the alpha proteasome gene family. A model for the early origin and evolution of the proteasome gene family is presented.

Base Sequence↗
PubMed1999

A genome scan for QTL influencing milk production and health traits in dairy cattle.

A genome scan was conducted in the North American Holstein-Friesian population for quantitative trait loci (QTL) affecting production and health traits using the granddaughter design. Resource families consisted of 1,068 sons of eight elite sires. Genome coverage was estimated to be 2,551 cM (85%) for 174 genotyped markers. Each marker was tested for effects on milk yield, fat yield, protein yield, fat percentage, protein percentage, somatic cell score, and productive herd life using analysis of variance. Joint analysis of all families identified marker effects on 11 chromosomes that exceeded the genomewide, suggestive, or nominal significance threshold for QTL effects. Large marker effects on fat percentage were found on chromosomes 3 and 14, and multimarker regression analysis was used to refine the position of these QTL. Half-sibling families from Israeli Holstein dairy herds were used in a daughter design to confirm the presence of the QTL for fat percentage on chromosome 14. The QTL identified in this study may be useful for marker-assisted selection and for selection of a refined set of candidate genes affecting these traits.

Animals↗
PubMed1999

Localization of the locus causing Spider Lamb Syndrome to the distal end of ovine Chromosome 6.

Spider Lamb Syndrome (SLS) is a semi-lethal congenital disorder, causing severe skeletal abnormalities in sheep. The syndrome has now been disseminated into several sheep breeds in the United States, Canada, and Australia. The mode of inheritance for SLS is autosomal recessive, making the identification and culling of carrier animals difficult due to their normal phenotype. Two large pedigrees segregating for the SLS mutation were established, and a genome scan with genetic markers from previously published genome maps of cattle and sheep was used to map the locus causing SLS. Genetic linkage between SLS and several microsatellite markers, OarJMP8, McM214, OarJMP12, and BL1038, was detected, thereby mapping the SLS locus to the telomeric end of ovine Chromosome (Chr) 6. Alignment of ovine Chr 6 with its evolutionary ortholog, human Chr 4, revealed a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3).

Animal Diseases↗
PubMed1999

Bovine chromosome 4 workshop: consensus and comprehensive linkage maps.

The report of the bovine chromosome 4 (BTA4) workshop is presented. Six laboratories contributed a total of 30,168 informative meioses from 62 loci. Twenty-two loci were typed by at least two independent laboratories and were used to construct a consensus linkage map of BTA4. The remaining 40 loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 131.4 cM. The female map was 124.3 cM in length, while the male map was 134.3 cM. The comprehensive sex-averaged map spanned 141.6 cM. The length of the female and male comprehensive maps were 123.1 cM and 156.4 cM, respectively. Average genetic distance between loci was 6 and 2.3 cM for the consensus and comprehensive linkage maps, respectively.

Animals↗
PubMed1999

Standardization and conversion of marker polymorphism measures.

Large scale gene mapping efforts in domestic animals have generated and mapped a large number of genetic markers that are useful for mapping quantitative trait and disease loci and for DNA diagnostic purposes such as parentage testing. Marker polymorphism is an important criterion for selecting genetic markers in planning experiment for mapping quantitative trait loci or for DNA diagnostic purposes. Current formulations of marker polymorphism measures are functions of marker allele frequencies. In this study, two measures of marker polymorphism that are available from gene mapping studies and do not require allele frequencies were proposed and analyzed: the observed polymorphic information content (PIC) and the observed family information content (FIC). The observed FIC was more stable than the observed PIC because the observed FIC is unaffected by the variation in the frequency of heterozygous parents. However, both FIC and PIC are dependent on the gene mapping design. The effective number of alleles is recommended as a tool to standardize marker polymorphism measures so that polymorphism of different markers can be compared on an equal basis, and to obtain a new polymorphism measure (such an exclusion probability) from an existing measure (such as FIC). The usage of the effective number of alleles to standardize FIC, PIC and exclusion probabilities is illustrated using genetic markers in a published linkage map.

Animals↗
PubMed1999

The callipyge phenomenon: evidence for unusual genetic inheritance.

In 1983, a male lamb exhibiting a pronounced muscular hypertrophy, particularly noticeable in the hind quarters, was born into a commercial Dorset flock in Oklahoma. The ram was premonitorily called Solid Gold. He subsequently produced offspring expressing the unusual phenotype, which is referred to as callipyge (Greek: calli- beautiful + -pyge buttocks). Animals demonstrating the callipyge phenotype are all descendants of this founder ram. These animals produce leaner, higher yielding carcasses, but there is some concern with decreased tenderness of the loin. Genetic characterization of the locus has demonstrated a unique mode of inheritance termed polar overdominance, in which only heterozygous offspring inheriting the mutation from their sire express the phenotype. The three other genotypes are normal in appearance. Progeny data indicate that reactivation of the maternal callipyge allele occurs after passage through the male germ line, although this reactivation is not absolute. The callipyge gene has been mapped to the distal end of ovine chromosome 18.

Animals↗
PubMed1998

Comparative analysis of 82 expressed sequence tags from a cattle ovary cDNA library.

In total, 82 ESTs were generated from 51 unique clones randomly selected from a cattle ovary cDNA library. Among these clones, 22 (42.1%) had 5' and/or 3' ends that matched with known human or other mammalian coding sequences, 18 (35.3%) matched human or other ESTs, and 11 (21.6%) represented novel transcripts with no significant match to any sequence in the databases. The relatively high frequency of ESTs with no matches in GenBank or dbEST indicates that bovine ovary may be a source of novel candidate genes for loci affecting cattle reproduction traits. Primers were designed for 11 ESTs that had human orthologs in GenBank. These ESTs were mapped to 10 bovine autosomes by PCR screening of a somatic cell hybrid panel. Among these 11 ESTs, 4 corresponded to genes previously mapped in humans and had chromosome assignments on the bovine map that were consistent with available comparative mapping data. Although the human orthologs of the remaining 7 mapped bovine ESTs have not been mapped, the human map location could be predicted on the basis of existing comparative mapping data. Because of the general utility of our approach for comparative genome analysis, we have termed it comparative mapping by annotation and sequence similarity (COMPASS). With the cost of large-scale EST sequencing becoming more affordable, and the rapid expansion of DNA databases, it is likely that COMPASS will be a preferred strategy for high throughput comparative mapping.

Animals↗
PubMed1998

Report of the first workshop on the genetic map of bovine chromosome 1.

A report of the first workshop on the genetic map of bovine chromosome 1 (BTA1) is presented. Five laboratories contributed 31,962 informative meioses from 70 loci. Thirty-two loci which had been typed by at least two laboratories were used to construct a framework genetic map with a likelihood ratio support of at least 1000:1 for locus order. The resulting sex-averaged framework map contained 26 loci and spanned 163.6 CM. The lengths of the female and male maps were 159.5 CM and 165.3 CM, respectively, and there was evidence for an expansion in the telomeric one-third of the male map. Of the four cases where order for closely linked loci differed among the maps produced for each of the contributing laboratories, a consensus order was obtained for three in the framework map. The average genetic distance between framework loci on the sex-averaged map was 6.3 CM.

Animals↗