RESUMO
Multiple ovulations are uncommon in humans, cattle and many breeds of sheep. Pituitary gonadotrophins and as yet unidentified ovarian factors precisely regulate follicular development so that, normally, only one follicle is selected to ovulate. The Inverdale (FecXI) sheep, however, carries a naturally occurring X-linked mutation that causes increased ovulation rate and twin and triplet births in heterozygotes (FecXI/FecX+; ref. 1), but primary ovarian failure in homozygotes (FecXI/FecXI; ref. 2). Germ-cell development, formation of the follicle and the earliest stages of follicular growth are normal in FecXI/FecXI sheep, but follicular development beyond the primary stage is impaired. A second family unrelated to the Inverdale sheep also has the same X-linked phenotype (Hanna, FecXH). Crossing FecXI with FecXH animals produces FecXI/FecXH infertile females phenotypically indistinguishable from FecXI/FecXI females. We report here that the FecXI locus maps to an orthologous chromosomal region syntenic to human Xp11.2-11.4, which contains BMP15, encoding bone morphogenetic protein 15 (also known as growth differentiation factor 9B (GDF9B)). Whereas BMP15 is a member of the transforming growth factor beta (TGFbeta) superfamily and is specifically expressed in oocytes, its function is unknown. We show that independent germline point mutations exist in FecXI and FecXH carriers. These findings establish that BMP15 is essential for female fertility and that natural mutations in an ovary-derived factor can cause both increased ovulation rate and infertility phenotypes in a dosage-sensitive manner.
Assuntos
Proteínas Morfogenéticas Ósseas/genética , Substâncias de Crescimento/genética , Infertilidade Feminina/genética , Peptídeos e Proteínas de Sinalização Intercelular , Mutação , Ovulação/fisiologia , Cromossomo X , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteína Morfogenética Óssea 15 , Proteínas Morfogenéticas Ósseas/química , Mapeamento Cromossômico , DNA Complementar , Feminino , Fator 9 de Diferenciação de Crescimento , Substâncias de Crescimento/química , Humanos , Masculino , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Oócitos/metabolismo , Linhagem , Conformação Proteica , OvinosAssuntos
Monoaminoxidase/genética , Polimorfismo de Fragmento de Restrição , Ovinos/genética , Cromossomo X , Animais , Sequência de Bases , Mapeamento Cromossômico , Primers do DNA , Desoxirribonucleases de Sítio Específico do Tipo II , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da PolimeraseAssuntos
Bovinos/genética , Mapeamento Cromossômico , Ovinos/genética , Animais , Cricetinae , Hexosaminidases/genética , Células Híbridas , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA-Redutases NADP-Dependentes , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T gama-delta/genéticaAssuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 1 , Ovinos/genética , Animais , Complexo CD3/genética , Cricetinae , Humanos , Células Híbridas , Fatores de Crescimento Neural/genética , Fosfoglucomutase/genética , ATPase Trocadora de Sódio-Potássio/genética , Tireotropina/genética , Urato Oxidase/genética , alfa-Amilases/genéticaRESUMO
Six loci, apoliproprotein B (including Ag(x) antigen), immunoglobulin kappa constant region (IGKC), luteinizing hormone/choriogonadotrophin receptor, avian myelocytomatosis viral related oncogene, neuroblastoma derived, ornithine decarboxylase, and proopiomelanocortin (adrenocorticotropin/beta-lipotropin) (POMC), were newly assigned to sheep chromosome 3p using a chromosomally characterized minipanel of sheep-hamster cell hybrids. Isotopic in situ hybridization of IGKC to sheep chromosome 3p22-p17 is reported, confirming the cell hybrid assignment. As these loci are all known to map to human chromosome 2p, this study demonstrates that this chromosomal segment is extensively conserved in sheep. Only POMC has been previously assigned to cattle chromosome 11, which is the equivalent of sheep chromosome 3p. Therefore, we predict that the other loci assigned in this study to sheep 3p are likely to be located on cattle 11. The provisional assignment of an additional locus, annexin-like to sheep chromosome 3p is also reported.
Assuntos
Mapeamento Cromossômico/veterinária , Cromossomos Humanos Par 2 , Ovinos/genética , Animais , Apolipoproteínas B/genética , Southern Blotting , Cricetinae , Genes myc , Humanos , Células Híbridas , Cadeias kappa de Imunoglobulina/genética , Hibridização In Situ , Ornitina Descarboxilase/genética , Pró-Opiomelanocortina/genética , Receptores do LH/genéticaRESUMO
Eight new loci have been assigned to sheep Chromosome (Chr) 1q by use of a chromosomally characterized minipanel of sheep x hamster cell hybrids. Four loci, which have been mapped to the distal region of human Chr 3q, are ceruloplasmin (CP), sucrase isomaltase (SI), glucose transporter 2 (GLUT2), and ectopic viral integration site 1 (EVI1). The other four loci, on human Chr 21, include interferon alpha receptor (IFNAR); interferon inducible protein p78, murine (MX1); collagen type VI, alpha 1 (COL6A1); and S100 protein, beta polypeptide (S100B). All of these loci, except GLUT2 and MX1, have been mapped onto bovine Chr 1 or are syntenic with loci on this chromosome. The in situ localization of transferrin (TF) to sheep Chr 1q42-q45 confirms our previous assignment of this locus and independently anchors the eight new syntenic loci to sheep Chr 1q.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 3 , Ovinos/genética , Animais , Bovinos , Cricetinae , Humanos , Células Híbridas , Hibridização In Situ , Proteínas/genética , Transferrina/genéticaRESUMO
Using a chromosomally characterized minipanel of sheep x hamster cell hybrids, five new loci, including carbonic anhydrase II (CA2), calbindin 1 (28 kDa) (CALB1), corticotropin releasing hormone (CRH), cytochrome P450 11B subfamily XIB (steroid-11-beta-hydroxylase), polypeptide 1 (CYP11B1), and interleukin 7 (IL7), have been assigned to sheep chromosome 9. A homolog of CA2 was detected on sheep chromosome 1. CRH was regionally localized to sheep 9q23-->q28 by in situ hybridization. This study assigns chromosome 9 as the sheep equivalent of cattle chromosome 14 and indicates that CALB1, CYP11B1, and IL7, which have not been mapped on the cattle genome, are likely to be present on cattle chromosome 14. It also shows by comparative genome analysis that a large segment of human chromosome 8q is highly conserved in sheep chromosome 9 and cattle chromosome 14. Based on these data, we propose that sheep chromosome 9 be recognised as the equivalent of cattle chromosome 14.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 8 , Hominidae/genética , Ovinos/genética , Animais , Calbindina 1 , Calbindinas , Anidrases Carbônicas/genética , Bandeamento Cromossômico , Hormônio Liberador da Corticotropina/genética , Cricetinae , Cricetulus , Sondas de DNA , DNA Complementar , Humanos , Células Híbridas , Hibridização In Situ , Interleucina-7/genética , Cariotipagem , Linfócitos/citologia , Proteína G de Ligação ao Cálcio S100/genética , Esteroide 11-beta-Hidroxilase/genéticaAssuntos
Apolipoproteínas B/genética , Polimorfismo Genético , Ovinos/genética , Alelos , Animais , Mapeamento Cromossômico/veterinária , Desoxirribonuclease HpaII , Desoxirribonucleases de Sítio Específico do Tipo II , Feminino , Frequência do Gene , Masculino , Linhagem , Polimorfismo de Fragmento de RestriçãoRESUMO
Seven new loci, casein alpha-S1 (CSN1S1), casein alpha-S2 (CSN1S2), casein beta (CSN2), the Hardy-Zuckerman 4 feline sarcoma viral (v-kit) oncogene homolog (KIT), albumin (ALB), phosphodiesterase cyclic GMP (rod receptor) beta polypeptide (PDEB), and complement component 1 (IF), were assigned to sheep Chromosome (Chr) 6 by Southern hybridization to a panel of chromosomally characterized sheep x hamster cell hybrids. By isotopic in situ hybridization, CSN2 was regionally localized to sheep Chr (OOV) 6q22-q31, anchoring this syntenic group of markers on to OOV6 and confirming its homology at a molecular and cytological level with cattle Chr 6. The assignment of these loci, from PDEB (located on human Chr 4p16.3) to IF (on HSA4q24-q25), and the observation that interleukin 2 (IL2, on HSA4q26-q27) and tryptophan 2,3-dioxygenase (TDO2, on HSA4q31) are not located on OOV6, is further evidence of the close evolutionary relationship of sheep and cattle and the conserved synteny in these species of this extensive region of human Chr 4. On the basis of this conserved synteny, and the similar G- and Q-banding patterns of this chromosome in cattle and sheep, we propose that this sheep chromosome be numbered as 6, not 4 as recommended by ISCNDA (1990).