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M H Kohn

Publications and source records attributed to M H Kohn.

7 recordsLinked to original sources
PubMed2000

A gene-anchored map position of the rat warfarin-resistance locus, Rw, and its orthologs in mice and humans.

The locus underlying hereditary resistance to the anticoagulant warfarin (symbol in the rat, Rw) was placed in relation to 8 positionally mapped gene-anchored microsatellite loci whose positions were known in the genome maps of the rat, mouse, and human. Rw segregated with the markers Myl2 (zero recombinants) and Itgam, Il4r, and Fgf2r (one recombinant each) during linkage analysis in a congenic warfarin- and bromadiolone-resistant laboratory strain of rats. Comparative ortholog mapping between rat, mouse, and human placed Rw onto mouse chromosome 7 at about 60 to 63 cM and onto one of the human chromosomes 10q25.3-26, 12q23-q24.3, and 16p13.1-p11. (Blood. 2000;96:1996-1998)

Animals↗
PubMed2000

Natural selection mapping of the warfarin-resistance gene.

In theory, genes under natural selection can be revealed by unique patterns of linkage disequilibrium (LD) and polymorphism at physically linked loci. However, given the effects of recombination and mutation, the physical extent and persistence of LD patterns in natural populations is uncertain. To assess the LD signature of selection, we survey variation in 26 microsatellite loci spanning an approximately 32-cM region that includes the warfarin-resistance gene (Rw) in five wild rat populations having resistance levels between 0 and 95%. We find a high frequency of heterozygote deficiency at microsatellite loci in resistant populations, and a negative association between gene diversity (H) and resistance. Contrary to previous studies, these data suggest that directional rather than overdominant selection may predominate during periods of intense anticoagulant treatment. In highly resistant populations, extensive LD was observed over a chromosome segment spanning approximately 14% of rat chromosome 1. In contrast, LD in a moderately resistant population was more localized and, in conjunction with likelihood ratios, allowed assignment of Rw to a 2. 2-cM interval. Within this genomic window, a diagnostic marker, D1Rat219, assigned 91% of rats to the correct resistance category. These results further demonstrate that "natural selection mapping" in field populations can detect and map major fitness-related genes, and question overdominance as the predominant mode of selection in anticoagulant-resistant rat populations.

Animals↗
PubMed1999

Estimating population size by genotyping faeces.

Population size is a fundamental biological parameter that is difficult to estimate. By genotyping coyote (Canis latrans) faeces systematically collected in the Santa Monica Mountains near Los Angeles, California, we exemplify a general, non-invasive method to census large mammals. Four steps are involved in the estimation. First, presumed coyote faeces are collected along paths or roadways where coyotes, like most carnivores, often defaecate and mark territorial boundaries. Second, DNA is extracted from the faeces and species identity and sex is determined by mitochondrial DNA and Y-chromosome typing. Third, hypervariable microsatellite loci are typed from the faeces. Lastly, rarefaction analysis is used to estimate population size from faecal genotypes. This method readily provides a point count estimate of population size and sex ratio. Additionally, we show that home range use paternity and kinship can be inferred from the distribution and relatedness patterns of faecal genotypes.

Animals↗
PubMed1999

Genomic assignment of the warfarin resistance locus, Rw, in the rat.

The locus responsible for resistance to the anticoagulants warfarin and bromadiolone (locus symbol Rw) was integrated into the rat (Rattus norvegicus) microsatellite genome map. Seventh-generation offspring of a segregating strain of rats heterozygous resistant to both compounds were tested with a blood-clotting-response (BCR) test. No recombination between resistance to warfarin and bromadiolone was observed, indicating a common genetic basis. No recombinants were found between Rw and D1Arb18 (Myl2) located at the MIT-microsatellite map position 95.90 (SHRSP x BN F2-cross) or 82.24 (FHH x ACI F2-cross). Resistance segregated in a ratio expected for single, dominant gene responses. An equal number of females and males were resistant, but females retained higher percentage blood coagulation activities (PCA) after anticoagulant administration. Partial synteny between rat, mouse, and human suggests that Myl2 may serve as anchor to map the Rw homologs in mouse and human.

Animals↗
PubMed1998

A genetic record of population isolation in pocket gophers during Holocene climatic change.

A long-standing question in Quaternary paleontology is whether climate-induced, population-level phenotypic change is a result of large-scale migration or evolution in isolation. To directly measure genetic variation through time, ancient DNA and morphologic variation was measured over 2,400 years in a Holocene sequence of pocket gophers (Thomomys talpoides) from Lamar Cave, Yellowstone National Park, Wyoming. Ancient specimens and modern samples collected near Lamar Cave share mitochondrial cytochrome b sequences that are absent from adjacent localities, suggesting that the population was isolated for the entire period. In contrast, diastemal length, a morphologic character correlated with body size and nutritional level, changed predictably in response to climatic change. Our results demonstrate that small mammal populations can experience the long-term isolation assumed by many theoretical models of microevolutionary change.

Biological Evolution↗
PubMed1998

Empirical evaluation of preservation methods for faecal DNA.

We evaluate the relative effectiveness of four methods for preserving faecal samples for DNA analysis. PCR assays of fresh faecal samples collected from free-ranging baboons showed that amplification success was dependent on preservation method, PCR-product size, and whether nuclear or mitochondrial DNA was assayed. Storage in a DMSO/EDTA/Tris/salt solution (DETs) was most effective for preserving nuclear DNA, but storage in 70% ethanol, freezing at -20 degrees C and drying performed approximately equally well for mitochondrial DNA and short (< 200 bp) nuclear DNA fragments. Because faecal DNA is diluted and degraded, repeated extractions from faeces may be necessary and short nuclear markers should be employed for genotyping. A review of molecular scatology studies further suggests that three to six faeces per individual should be collected.

Animals↗