This work is the continuation of a systematic and detailed investigation of the repertoire of genomic variation harbored by a single mammalian species--the mouse Mus musculus. Genomic libraries constructed from a set of inbred and characterized strains of mice will serve as the basis for three distinct investigations: Gene conversion: The tandemly duplicated adult Beta-globin genes of the C57BL mouse, Betas and Betat, are over 99% homologous as the result of a gene conversion. The hypothesis that homology has been maintained by repeated gene conversion will be tested by cloning and sequencing the adult Beta-globin genes from other strains of mice that have Beta-globin gene clusters similar to, but not identical with, of C57BL. The sequence of these different converted intervals will clarify how the conversion process acts in rectifying genes by providing examples of very recent conversions, whose details have not been obscured by unrelated mutations. Recombination and rearrangements within Alpha-globin gene families: Even the simplest model for the evolutionary relationship of the eight Alpha-globin haplotypes identified in the mouse involves, in addition to ordinary replacement changes, two different instances of either gene conversion or gene silencing, and one instance of extragenic recombination characterization of these eight haplotypes will define the details of the recombinations and rearrangements by which they were derived. Concerted evolution of LINE elements: The concerted evolution of the long interspersed repetitive elements (LINEs) may reflect the fact that these elements are continually being strewn about the genome, through an RNA intermediate, from a small number of transcriptionally active """"""""mother"""""""" LINEs. A putative nascent, newly inserted LINE element will be used as a source of hybridization probes to isolate, under conditions of high stringency, other very homologous and hence recently dispersed LINEs. Fragments from the single-copy DNA that flanks these elements will be used as insertion-site probes to see whether, as expected, the mouse species is polymorphic with respect to putative nascent LINEs. Finally, these same probes will be used to screen a cDNA library for a transcript of the """"""""mother"""""""" LINE.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030140-05
Application #
3277745
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1982-02-01
Project End
1988-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Erhart, M A; Piller, K; Weaver, S (1987) Polymorphism and gene conversion in mouse alpha-globin haplotypes. Genetics 115:511-9
Holdener-Kenny, B; Weaver, S (1986) A naturally occurring deletion in the mouse Hbbs beta-globin gene cluster. Proc Natl Acad Sci U S A 83:4374-8
Shyman, S; Weaver, S (1985) Chromosomal rearrangements associated with LINE elements in the mouse genome. Nucleic Acids Res 13:5085-93
Erhart, M A; Simons, K S; Weaver, S (1985) Evolution of the mouse beta-globin genes: a recent gene conversion in the Hbbs haplotype. Mol Biol Evol 2:304-20