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United States Department of Agriculture

Agricultural Research Service

Title: Refinement of Bovine Chromosome 2 Linkage Map Near the Mh Locus Reveals Complex Rearrangements Between the Bovine and Human Genomes.

Authors
item Sonstegard, Tad
item Kappes, Steven
item Keele, John
item Smith, Timothy

Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 5, 1998
Publication Date: N/A

Interpretive Summary: The locus responsible for the appearance of muscular hypertrophy (mh) in double muscled cattle breeds has recently been shown to encode a secreted growth factor designated myostatin. This conclusion was based in part on the placement of myostatin in the interval to which mh had been mapped. During the mapping phase of our study, numerous yeast artificial chromosome (YAC) clones were isolated containing genetic markers closely linked to mh. Other YACs and cosmids were identified containing genes selected from comparative maps of the bovine and human genomes, with the goal of defining the position of breakpoints in conserved synteny between the human and bovine maps, thus permitting the accurate selection of positional candidate genes. An efficient sub-cloning procedure was developed to obtain microsatellites from YAC clones, to increase the number of informative meioses in the herds segregating mh and to place three new positional candidate genes on the cattle map. Twenty-three informative markers were developed, and seven were linked to BTA2, which contains the mh locus, improving marker density and informativeness at the centromeric end. Overall, the complexity of gene order rearrangements between mammalian genomes such as that observed between closely linked HSA2q genes compared to BTA2 and BTA11 emphasizes the importance of creating dense comparative maps between species, in order to efficiently utilize the wealth of human map information for functional genomics research in livestock.

Technical Abstract: The locus responsible for the appearance of muscular hypertrophy (mh) in double muscled cattle breeds has recently been shown to encode a secreted growth factor designated myostatin (MSTN). This conclusion was based in part on the placement of MSTN in the interval to which mh had been mapped. During the mapping phase of the study, numerous yeast artificial chromosome e(YAC) clones were isolated containing genetic markers closely llinked to mh. Other YACs and cosmids were identified containing genes selected from comparative maps of the bovine and human genomes, with the goal of defining the position of breakpoints in conserved synteny between the maps of these species, thereby permitting accurate selection of positional candidate genes. An efficient sub-cloning procedure was developed to obtain microsatellites (ms) from YAC clones, to increase the number of informative meioses in herds segregating for mh and to place the human orthologues of engrailed-1 (EN1), interleukin 1 beta (IL1B), and paired-box containing 8 (PAX8) genes on the cattle map. Twenty-three of 28 ms identified from YAC sub-clone libraries were informative in the mapping families. Seven were linked to BTA2, which contains the mh locus, improving marker density and informativeness at the centromeric end. The two MSTN and four EN1 gene associated ms markers developed from YACs, map 1.5 and 61.6 cM on the BTA2 linkage group, respectively. In addition, ms markers developed from cosmids containing either IL1B or PAX8, map to 56.6 and 56.9 cM on the BTA11 linkage group, respectively. This linkage data confirms the location and/or orientation of orthologous segments of human chromosome 2q that were previously indistinguishable on the bovine map, and demonstrates the presence of micro-rearrangements of gene order and conserved synteny.

Last Modified: 4/23/2014
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