RESUMO
Hitherto, the only known mutant gene leading to the long-hair phenotype in mammals is the fibroblast growth factor 5 (FGF5). In many dog breeds, the previously discovered FGF5:p.Cys95Phe mutation appeared completely concordant with the long-hair phenotype, but for some breeds, the long-hair phenotype could not be resolved. First, we studied the role of the FGF5:p.Cys95Phe and FGF5:g.145_150dupACCAGC mutations in 268 dogs descending from 27 breeds and seven wolves. As these mutations did not explain all the long-hair phenotypes, all exons and their neighbouring regions of FGF5 were re-sequenced. We detected three novel mutations in the coding sequence and one novel non-coding splice-site mutation in FGF5 associated with the long-hair phenotype. The FGF5:p.Ala193Val polymorphism was perfectly consistent with long hair in Akitas and probably in Siberian huskies, too. Dogs of the long-hair breed Samoyed were either homozygous or compound heterozygous for the FGF5:p.Ala193Val or the FGF5:p.Cys95Phe polymorphisms respectively. The two newly detected polymorphisms FGF5:c.559_560dupGG and FGF5:g.8193T>A and the known mutation FGF5:p.Cys95Phe explained the long-hair phenotype of all Afghan hounds analysed. An FGF5:c.556_571del16 mutation was found in one longhaired Eurasier. All long-hair-associated mutations follow a recessive mode of inheritance, and allelic heterogeneity was a common finding in breeds other than Akita.
Assuntos
Cães/genética , Fator 5 de Crescimento de Fibroblastos/genética , Cabelo/crescimento & desenvolvimento , Polimorfismo Genético/genética , Animais , DNA Complementar/química , DNA Complementar/genética , Cães/crescimento & desenvolvimento , Frequência do Gene , Heterogeneidade Genética , Dados de Sequência Molecular , Mutação , Fenótipo , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA/veterinária , Especificidade da EspécieRESUMO
Left-sided displacement of the abomasum (LDA) is one of the most common disorders of the digestive system in many dairy breeds and particularly in Holstein dairy cows. We performed a genome-wide association study for 854 German Holstein cows, including 225 cases and 629 controls. All cows were genotyped using the Illumina Bovine SNP50 BeadChip (Illumina Inc., San Diego, CA). After quality control of genotypes, a total of 36,226 informative single nucleotide polymorphisms (SNP) were left for analysis. We used a mixed linear model approach for a genome-wide association study of LDA. In total, 36 SNP located on 17 bovine (Bos taurus) chromosomes (BTA) showed associations with LDA at nominal -log10P-values >3.0. Two of these SNP, located on BTA11 at 46.70 Mb and BTA20 at 16.67 Mb, showed genome-wide significant associations with LDA at -log10P-values >4.6. Pathway analyses indicated genes involved in calcium metabolism and insulin-dependent diabetes mellitus to be factors in the pathogenesis of LDA in German Holstein cows.
Assuntos
Abomaso/anormalidades , Doenças dos Bovinos/genética , Bovinos/genética , Estudo de Associação Genômica Ampla/veterinária , Animais , Cruzamento , Feminino , Genótipo , Alemanha , Polimorfismo de Nucleotídeo ÚnicoRESUMO
PURPOSE: Bilateral convergent strabismus with exophthalmos (BCSE) is a widespread inherited eye defect in several cattle populations. Its progressive condition often leads to blindness in affected cattle and shortens their length of productive life. Furthermore, breeding with BCSE-affected animals is forbidden by the German animal welfare laws. We performed a mutation and association analysis for three candidate genes (troponin T type 1 [TNNT1], retinol dehydrogenase 13 [RDH13], and TCF3 fusion partner [TFPT]), which are located within the previously identified BCSE-linked region on the telomeric end of bovine chromosome 18 (BTA18). In addition, we developed single nucleotide polymorphisms (SNPs) within these three candidate genes and nine other genes that are contained in this genomic BCSE-region to perform association analyses with BCSE in German Brown cattle. METHODS: We performed cDNA analyses of all three candidate genes using eye tissues of three affected German Brown cows and three unaffected controls. Furthermore, we screened the exonic and the adjacent genomic sequences of RDH13, TNNT1, and TFPT using four BCSE-affected and four controls of German Brown cattle. Here, we included all exons of RDH13 and those exons of TNNT1 and TFPT for which SNPs were detected by cDNA analyses. In addition, we developed 21 polymerase chain reaction (PCR) products for 17 more genes in the BCSE region and searched them for polymorphisms. All markers detected were genotyped in 48 BCSE-affected German Brown cows and 48 breed and sex matched controls and tested for association with BCSE. RESULTS: In total, we detected 29 SNPs in 12 genes. In the coding sequence of the three candidate genes, we identified 10 exonic SNPs and a new splice variant of TNNT1. Four SNPs were associated with the BCSE phenotype in single marker-trait analyses. These SNPs were located within DHDH (dihydrodiol dehydrogenase dimeric), CPT1C (carnitine palmitoyltransferase 1C), TNNT1, and NALP7. The marker-trait association for haplotypes including five SNPs of CPT1C, SYT5 (synaptotagmin V), RDH13, and NALP7 (NLR family, pyrin domain containing 7) revealed a significant association with BCSE. We identified three individual haplotypes that were significantly associated with BCSE. These haplotypes spanned the region from 56.05 Mb to 62.87 Mb on BTA18. CONCLUSIONS: The haplotype association analysis corroborated the results of the linkage study that the telomeric end of BTA18 harbors a gene responsible for BCSE and further refines the BCSE region to a 6.82 Mb interval ranging from 56.05 Mb to 62.87 Mb on BTA18.
Assuntos
Bovinos/genética , Cromossomos de Mamíferos/genética , Esotropia/complicações , Esotropia/genética , Exoftalmia/complicações , Exoftalmia/genética , Predisposição Genética para Doença , Oxirredutases do Álcool/química , Oxirredutases do Álcool/genética , Processamento Alternativo/genética , Sequência de Aminoácidos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Análise Mutacional de DNA , Proteínas do Olho/química , Proteínas do Olho/genética , Frequência do Gene , Genoma Humano/genética , Alemanha , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , Alinhamento de Sequência , Sintenia/genéticaRESUMO
Bilateral convergent strabismus with exophthalmus (BCSE) is a widespread inherited eye defect in several cattle populations. Its progressive condition often leads to blindness in affected cattle and decreases their usability. Furthermore, the German animal welfare laws prevent breeding with animals whose progeny are expected to be affected by genetic defects. Identifying genes involved in the heredity of BCSE should lead to insights into the molecular pathogenesis of this eye disease and permit the establishment of a genetic test for this disease. A whole-genome scan for 10 families containing a total of 159 genotyped individuals identified two BCSE loci. One BCSE locus mapped to the centromeric region on bovine chromosome (BTA) 5 and the other BCSE locus mapped to the telomeric region of BTA18. Thus, it is possible that two genes are involved in the development of BCSE. Alternatively, one of these loci could be the cause for the development of BCSE and the other locus could affect the progression and severity of the defect.
Assuntos
Doenças dos Bovinos/genética , Cromossomos de Mamíferos , Esotropia/veterinária , Exoftalmia/veterinária , Predisposição Genética para Doença , Animais , Bovinos , Mapeamento Cromossômico , Esotropia/genética , Exoftalmia/genética , Feminino , Masculino , Repetições de Microssatélites , Linhagem , Gravidez , Locos de Características QuantitativasRESUMO
A whole-genome scan using an affected paternal half-sib design was utilized to detect quantitative trait loci (QTL) for left-sided displaced abomasum (LDA) in German Holsteins. A total of 360 animals from 14 paternal half-sib families were genotyped, for a total of 306 polymorphic microsatellites. For a whole-genome scan, 221 markers were equally distributed over all 29 bovine autosomes, with an average distance of 13.7 cM. For fine-mapping, a total of 85 additional microsatellites were used. We identified genome-wide significant QTL on Bos taurus autosome (BTA) 1 (54.6 to 58.3 cM) and on BTA3 (5.9 cM). Furthermore, 3 chromosome-wide significant QTL were located on bovine chromosomes 21, 23, and 24. In addition, we found 11 QTL that cosegregated in grandsire families but that were not significant in the across-family analysis. These QTL were located on BTA5, 6, 10, 12, 15, 16, 17, 19, 23, and 26. This study is the first report on QTL for LDA and is a first step toward identifying single nucleotide polymorphisms for LDA-QTL.
Assuntos
Abomaso/anormalidades , Doenças dos Bovinos/genética , Mapeamento Cromossômico , Locos de Características Quantitativas/genética , Gastropatias/veterinária , Animais , Bovinos , Indústria de Laticínios , Feminino , Genoma/genética , Alemanha , Masculino , Repetições de Microssatélites/genética , Gastropatias/genéticaRESUMO
The mammalian ATP2A2 gene encodes a P-type cation pump located in the sarcoplasmic or endoplasmic reticula of muscle cells. We isolated one bacterial artificial chromosome (BAC) clone containing the equine ATP2A2 gene and determined the complete coding sequence of this gene. Cloning and characterization of the equine ATP2A2 gene revealed that the equine ATP2A2 gene consists of 20 exons. In total, 32 horses out of 16 breeds were analyzed for single nucleotide polymorphisms (SNPs). A mutation scan for SNPs included ten exons and their flanking introns. We detected in total 17 SNPs, 14 of which were located in introns, one in exon 9 and two in exon 20. In this report we provide the genomic organization and the equine ATP2A2 coding sequence and an association analysis for chronic pastern dermatitis using a sample of South German draft horses.
Assuntos
Cavalos/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , DNA Intergênico/genética , Éxons/genética , Humanos , Íntrons/genética , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/química , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
In this study, we present a comprehensive 5000-rad radiation hybrid map of a 40-cM region on equine chromosome 4 (ECA4) that contains quantitative trait loci for equine osteochondrosis. We mapped 29 gene-associated sequence tagged site markers using primers designed from equine expressed sequence tags or BAC clones in the ECA4q12-q22 region. Three blocks of conserved synteny, showing two chromosomal breakpoints, were identified in the segment of ECA4q12-q22. Markers from other segments of HSA7q mapped to ECA13p and ECA4p, and a region of HSA7p was homologous to ECA13p. Therefore, we have improved the resolution of the human-equine comparative map, which allows the identification of candidate genes underlying traits of interest.
Assuntos
Cavalos/genética , Mapeamento de Híbridos Radioativos , Animais , Cromossomos Artificiais Bacterianos , Cromossomos de Mamíferos , Etiquetas de Sequências Expressas , Doenças dos Cavalos/genética , Humanos , Repetições de Microssatélites , Osteocondrite/genética , Osteocondrite/veterinária , Locos de Características Quantitativas , SinteniaRESUMO
In this study we present a comprehensive 3000-rad radiation hybrid map on bovine chromosome 5 (BTA5) of a region between 12.8 and 74.0 cM according to the linkage map, which contains a quantitative trait loci for ovulation rate. We mapped 28 gene-associated sequence tagged site markers derived from sequences of bovine BAC clones and 10 microsatellite markers to the BTA5 region. In comparison with HSA12q, four blocks of conserved synteny were apparent showing three chromosomal breakpoints and two inversions in this segment of BTA5. Therefore, we have improved breakpoint resolution in the human-bovine comparative map, which enhances the determination of candidate genes underlying traits of interest mapped to BTA5.
Assuntos
Bovinos/genética , Cromossomos Humanos Par 12/genética , Cromossomos de Mamíferos/genética , Mapeamento de Híbridos Radioativos , Animais , Biologia Computacional , Primers do DNA , Bases de Dados de Ácidos Nucleicos , Eletroforese em Gel de Ágar , Feminino , Humanos , Escore Lod , Repetições de Microssatélites/genética , Ovulação/genética , Reação em Cadeia da Polimerase , Locos de Características Quantitativas , Sitios de Sequências RotuladasRESUMO
Genome-wide scans have mapped economically important quantitative trait loci (QTL) for mastitis susceptibility in dairy cattle at the telomeric end of bovine chromosome 18 (BTA18). In order to increase the density of markers in this chromosomal region and to improve breakpoint resolution in the human-bovine comparative map, this study describes the chromosomal assignment of seven newly developed gene-associated markers and five microsatellites and eight previously mapped sequence tagged site markers near these QTL. The orientation of KCNJ14, BAX, CD37, NKG7, LIM2, PRKCG, TNNT1, MGC2705, RPL28, EPN1, ZNF582, ZIM2, STK13, ZNF132 and SLC27A5 on the 3000-rad radiation hybrid (RH) map of BTA18 is homologous to the organization found on the corresponding 10 Mbp of human chromosome 19q (HSA19q). The resulting bovine RH map with a length of 20.9 cR spans over about 11 cM on the bovine linkage map. The location of KCNJ14 and SLC27A5 flanking the RH map on BTA18q25-26 has been confirmed by fluorescence in situ hybridization. The data of this refined human-bovine comparative map should improve selection of candidate genes for mastitis susceptibility in dairy cattle.