Short tandem repeat polymorphic markers for the rat genome from marker-selected libraries

Abstract. In an effort to generate a genome-wide set of high-quality polymorphic markers for the rat, we used the marker-selection method, which has already been proven useful for the development of markers, especially for the human genome. Small-insert (300–900 bp) rat genomic libraries were constructed with an estimated complexity of three genome equivalents and enriched for short tandem repeat sequences (STRs). The enriched libraries were found to contain 45% (CA)n and 27% (GATA)n, representing at least a 50-fold enrichment over unselected small insert genomic libraries. A subset of 2160 STR-containing clones, primarily of the (GATA)n class of repeats, were sequenced. PCR primers flanking the repeats were synthesized from some of the sequences from the (CA)n and (GATA)n classes of STRs and tested for polymorphism in a panel of eight inbred rat strains. This strategy yielded 147 polymorphic markers, which mapped with high odds to all chromosomes by linkage in three F2 populations. The integration of these STR markers with other rat genetic markers and mapping reagents will facilitate the mapping of disease genes in the rat and the identification of loci associated with complex mammalian phenotypes.

[1]  V. Sheffield,et al.  Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic linkage mapping and analysis of a balanced translocation breakpoint. , 1997, Human molecular genetics.

[2]  S. Lincoln.  Constructing genetic maps with MAPMAKER/EXP 3.0. , 1992 .

[3]  Y. Hosoya,et al.  A rat genetic map constructed by representational difference analysis markers with suitability for large-scale typing. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Daly,et al.  MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. , 1987, Genomics.

[5]  M. Bihoreau,et al.  An improved linkage map of rat Chromosome 3 with three mapping panels , 1998, Mammalian Genome.

[6]  K H Buetow,et al.  A collection of tri- and tetranucleotide repeat markers used to generate high quality, high resolution human genome-wide linkage maps. , 1995, Human molecular genetics.

[7]  V. Sheffield,et al.  Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling. , 1997, Human molecular genetics.

[8]  M. Bihoreau,et al.  A linkage map of the rat genome derived from three F2 crosses. , 1997, Genome research.

[9]  V. Sheffield,et al.  Use of a DNA pooling strategy to identify a human obesity syndrome locus on chromosome 15. , 1995, Human molecular genetics.

[10]  K. Klinga-Levan,et al.  Gene Map of the Rat , 1993 .

[11]  J. Rine,et al.  Construction of small-insert genomic DNA libraries highly enriched for microsatellite repeat sequences. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Weber,et al.  Survey of human and rat microsatellites. , 1992, Genomics.

[13]  T. Kurtz,et al.  Linkage of 11β-hydroxylase mutations with altered steroid biosynthesis and blood pressure in the Dahl rat , 1993, Nature Genetics.

[14]  E. Remmers,et al.  Linkage map of nine loci defined by polymorphic DNA markers assigned to rat chromosome 13. , 1993, Genomics.

[15]  M. Festing,et al.  Inbred strains of rats , 1981, Behavior genetics.

[16]  J. Rapp,et al.  Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt–sensitive rats , 1992, Nature Genetics.

[17]  G. Lathrop,et al.  Rat gene mapping using PCR-analyzed microsatellites. , 1992, Genetics.

[18]  V. Sheffield,et al.  A cerebellar ataxia locus identified by DNA pooling to search for linkage disequilibrium in an isolated population from the Cayman Islands. , 1996, Human molecular genetics.

[19]  B J Bassam,et al.  Fast and sensitive silver staining of DNA in polyacrylamide gels. , 1991, Analytical biochemistry.

[20]  J. Weber,et al.  Survey of trinucleotide repeats in the human genome: assessment of their utility as genetic markers. , 1995, Human molecular genetics.

[21]  G. Levan,et al.  The gene map of the Norway rat (Rattus norvegicus) and comparative mapping with mouse and man. , 1991, Genomics.

[22]  G. Levan,et al.  Gene map of the rat (Rattus norvegicus) 2N = 42. , 1990 .

[23]  R. Ridgway,et al.  Isolation of high-molecular-weight DNA from insects. , 1990, Analytical biochemistry.

[24]  B. Hoebee,et al.  Mapping of rat Chromosome 2 markers generated from chromosome-sorted DNA , 1997, Mammalian Genome.

[25]  E. Lander,et al.  An integrated genetic linkage map of the laboratory rat , 1998, Mammalian Genome.

[26]  V. Sheffield,et al.  Identification of a Bardet-Biedl syndrome locus on chromosome 3 and evaluation of an efficient approach to homozygosity mapping. , 1994, Human molecular genetics.

[27]  J C Murray,et al.  Pediatrics and , 1998 .

[28]  M. Daly,et al.  A genetic linkage map of the laboratory rat, Rattus norvegicus , 1995, Nature Genetics.

[29]  M. Garrett,et al.  Genome scan and congenic strains for blood pressure QTL using Dahl salt-sensitive rats. , 1998, Genome research.