Comparative mapping of the ovine clpg locus

Abstract

Abstract. We used a comparative mapping approach to identify segments of conserved synteny between human Chromosome 14 (HSA14), bovine Chromosome 21 (BTA21), and the portion of ovine Chromosome 18 (OAR18) that contains the clpg locus. A bovine radiation hybrid map of the region was constructed with available Type II genetic markers and seven candidate genes to establish the comparative interval between BTA21 and HSA14. We developed polymorphic microsatellite and SNP markers associated with five candidate genes and placed them on the ovine and/or bovine genetic maps by multipoint linkage analysis. Three additional genes were mapped by virtue of their physical linkage to genetically mapped makers. Development of integrated linkage and physical maps facilitates the selection of positional candidate genes from the gene rich human map. The physically linked candidate genes PREF-1 and MEG3 map to the interval containing the clpg locus. Comparative biology suggests imprinting of MEG3 and/or the influences of PREF-1 on cellular differentiation, should be examined for their role in the parent-of-origin dependent influence of mutant clpg alleles on sheep muscle characteristics.

Novel Imprinted DLK1/GTL2 Domain on Human Chromosome 14 Contains Motifs that Mimic Those Implicated in IGF2/H19 Regulation

“…Although CLPG has not yet been identified, this locus has been tightly linked to sheep distal chromosome 18, which is homologous with regions in mice (distal 12) and humans (distal 14q) known to harbor imprinted genes. Using a comparative mapping approach, Fahrenkrug et al (2000) have recently mapped the CLPG locus to an interval containing DLK1 and GTL2. The paternal expression of DLK1, combined with its chromosomal location and role as a negative regulator of adipocyte differentiation, is consistent with the postulate that mutations affecting the ovine ortholog of DLK1 are responsible for the CLPG phenotype in sheep.…”

Identification of the Single Base Change Causing the Callipyge Muscle Hypertrophy Phenotype, the Only Known Example of Polar Overdominance in Mammals

“…It was postulated that single nucleotide polymorphisms (SNPs) heterozygous in affected and homozygous for alternative alleles in NN and CC animals were candidates for the causative mutation. Areas containing coding regions of previously identified candidate genes (DLK1, MEG3; Fahrenkrug et al 2000) were first sequenced in these animals. Although polymorphisms were detected, none uniquely differentiated the CLPG alleles.…”

Human–Ovine Comparative Sequencing of a 250-kb Imprinted Domain Encompassing the Callipyge (clpg) Locus and Identification of Six Imprinted Transcripts: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8

“…As part of a positional cloning effort, we and others have mapped the clpg locus by linkage analysis to the 4 cM IDVGA30-OY3 interval on distal OAR18q (Fahrenkrug et al 2000;Shay et al 2001), constructed an ovine BAC contig spanning that interval , and refined the map position of the clpg locus by breakpoint analysis to a Յ400 kb chromosome segment flanked by microsatellite markers MULGE5 and OY3 ). The same interval was shown to contain the DLK1 and GTL2 genes, which were recently demonstrated to be reciprocally imprinted in the mouse and human: DLK1 being expressed from the paternal allele and GTL2 from the maternal allele (Miyoshi et al 2000;Schmidt et al 2000;Takada et al 2000;Wylie et al 2000).…”