Mapping of dentin-specific acidic phosphoprotein and integrin-binding sialoprotein in sheep defines an inversion breakpoint with respect to human chromosome 4Q

Abstract

Genes from sheep chromosome 6 map to human chromosome 4 in the region extending from 4p16 to 4q26. However, there is an inversion of gene order in the central portion of the chromosome with one breakpoint close to secreted phosphoprotein 1 (SPP1). Genes for SPP1, integrin-binding sialoprotein (IBSP) and dentin-specific acidic phosphoprotein (DMP1) are located close together in a YAC contig in the human. RFLP markers were developed for DMP1 and IBSP in sheep and located on the sheep linkage map to further define the breakpoint region. There were no recombinants between SPP1 and IBSP indicating that these loci are close together in sheep, as in humans. DMP1 was located approximately 80 cM from SPP1 in sheep, 7 cM from the microsatellite BMC4203. In the human YAC contig, the order of these genes is SPP1-IBSP-DMP1 with 340 kb separating SPP1 and IBSP and 150 kb between IBSP and DMP1. Therefore, one breakpoint for the inversion in gene order between the sheep and the human has been narrowed to a region of 150 kb on the human map.<br>Gens do cromossomo 6 de carneiro ocupam posição similar no cromossomo 4 humano na região que vai de 4p16 a 4q26. Contudo, há uma inversão na ordem dos gens na porção central do cromossomo, com um ponto de quebra próximo à fosfoproteína 1 secretada (SPP1). Os gens para SPP1, sialoproteína ligada a integrina (IBSP) e fosfoproteína ácida dentina-específica (DMP1) estão localizados muito próximos em um contig YAC em humanos. Marcadores para RFLP foram desenvolvidos para DMP1 e IBSP em carneiros e localizados no mapa de ligações para posterior definição da região do ponto de quebra. Não houve recombinantes entre SPP1 e IBSP, indicando que esses loci estão intimamente relacionados no carneiro, como em humanos. DMP1 se localizou a aproximadamente 80 cM do SPP1 no carneiro e a 7 cM do microsatélite BMC4203. No contig YAC humano, a ordem desses gens é SPP1 - IBSP - DMP1, com 340 kb separando SPP1 de IBSP e 150 kb entre IBSP e DMP1. Portanto, um ponto de quebra para a inversão na ordem do gene do carneiro em relação ao homem foi reduzido para uma região de 150 kb no mapa humano

Genes controlling ovulation rate in sheep

“…There is a large inversion in gene order between sheep chromosome 6 and human chromosome 4 near the region of the FecB locus (Lord et al, 1996). The breakpoint for one end of the inversion has been mapped to a small region of 150 kb pairs between the genes for SPP1 (secreted phosphoprotein 1) and DMP1 (dentin-specific acidic phosphoprotein) (Lumsden et al, 1999) outside the critical region for the FecB locus. Data on genes in the critical region from the human gene maps and the annotated human DNA sequence will provide information for positional cloning.…”

“…However, the total number of antral follicles (у 1 mm diameter) was found to be greater in adult I+ ewes than in ++ ewes (Shackell et al, 1993;McNatty et al, 1995b). This difference was due to the presence of more small antral (Lord et al, 1996;Lumsden et al, 1999) showing the location for the FecB locus together with the major phenotype for heterozygous (B+) and homozygous (BB) carriers of the mutation. Gene loci are shown in blue and microsatellite markers in black.…”

Human twinning is not linked to the region of chromosome 4 syntenic with the sheep twinning geneFecB

“…The FecB locus is an important candidate for a DZT gene in humans. In sheep, the FecB locus maps to chromosome 6 between the alcohol dehydrogenase cluster and secreted phosphoprotein 1 [SPP1; Montgomery et al, 1993; Lord et al, 1996; Lumsden et al, 1999]. Comparative mapping has established that human chromosome 4 from 4p16 to 4q26 is syntenic with sheep chromosome 6 [Lord et al, 1996], although gene order is not conserved.…”

“…On sheep chromosome 6, the region from platelet derived growth factor receptor, alpha polypeptide (PDGFRA), to bone morphogenetic protein 3 (BMP3) appears to be inverted with respect to SPP1 on human chromosome 4 [Lord et al, 1996]. Dentin‐specific acidic phosphoprotein (DMP1) has recently been mapped in sheep and is located approximately 70 cM distal to SPP1 [Lumsden et al, 1999]. In contrast, DMP1 maps close to SPP1 in the human, within the same yeast artificial chromosome approximately 470 kb from SPP1 [Aplin et al, 1995].…”

“…In contrast, DMP1 maps close to SPP1 in the human, within the same yeast artificial chromosome approximately 470 kb from SPP1 [Aplin et al, 1995]. The location of DMP1 in the two species defines the inversion breakpoint close to SPP1 and just outside the critical region for the FecB locus [Lumsden et al, 1999]. Comparing maps from the human and the sheep, the region most likely to contain the human homologue for the FecB locus is a 16 cM region from D4S231 to D4S411 (Fig.…”