Evidence for increased recombination near the human insulin gene: implication for disease association studies.

Chakravarti, Aravinda; Elbein, Steven C.; Permutt, M. A.

doi:10.1073/pnas.83.4.1045

Cited by 87 publications

(54 citation statements)

References 32 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In those genes in which linkage disequilibrium has been studied, the degree of disequilibrium has correlated poorly with physical distance (20). Nonetheless, the small distance and relatively recent propagation of these RFLPs would suggest increased recombination at this locus (18). Interestingly, those pairs showing significant nonrandom association are present only in Caucasian and American Black populations and thus may be of more recent origin.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Multiple restriction fragment length polymorphisms at the insulin receptor locus: a highly informative marker for linkage analysis.

Elbein¹,

Corsetti²,

Ullrich³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Although resistance to insulin action is a well-studied phenomenon in non-insulin-dependent diabetes and certain genetic syndromes, the role of inherited defects of the insulin receptor in these disorders is unknown. To facilitate the evaluation of that role, restriction fragment length polymorphisms (RFLPs) were identified using various portions of the insulin receptor cDNA to examine digested DNA from American Blacks, Pina Indians, and Caucasians. Five RFLPs were identified in Caucasians. Two of these were detected with a single 1.3-kilobase probe in Rsa I digests with minor allele frequencies of 0.48 and 0.23. An additional RFLP was noted with Bgl H and two more RFLPs with Sac I using a different 1.6-kilobase probe, with minor allele frequencies of 0.17 for Bgl II and 0.12 for both Sac I RFLPs. All RFLPs except for the second Sac I RFLP were present in American Blacks, while only the Rsa I RFLPs were present in Pima Indians. Pairwise analysis showed random association between all sites except for the Bgl II and second Rsa I sites, where the disequilibrium statistic, A, was -0.70 (different from 0 at P < 0.001). No association of any RFLP was noted with non-insulin-dependent diabetes in a small population. These studies show that this is a highly informative locus that should be important for mapping of chromosome 19p and for linkage studies.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Initial screening for DNA polymorphisms was performed in a panel of [10][11][12][13][14][15][16][17][18][19][20] Caucasian and American Black individuals using two probes, 12 (14). Blots were subsequently washed and rescreened with probes derived from HIR 12.1 ( Fig.…”

Section: Methodsmentioning

confidence: 99%

Multiple restriction fragment length polymorphisms at the insulin receptor locus: a highly informative marker for linkage analysis.

Elbein¹,

Corsetti²,

Ullrich³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The four SNPs were in substantial but incomplete linkage disequilibrium (Table 3), consistent with the short distance between the most 5′ and most 3′ SNP. The lack of significant linkage disequilibrium between SNPs 2 and 3 might represent a recombination hotspot introduced by the microsatellite repeat [40].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of apolipoprotein A-II as a positional candidate gene for familial Type II diabetes, altered lipid concentrations, and insulin resistance

Chu

Ren

et al. 2002

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. We hypothesized that apolipoprotein A-II sequence variation was responsible for the observed linkage of Type II (non-insulin-dependent) diabetes mellitus to the apolipoprotein A-II region in Northern European families ascertained for multiple diabetic siblings, and might also influence insulin sensitivity and secretion, non-esterified fatty acids, and lipids. Methods. We recruited 698 members of 63 families for pedigree studies and additional unrelated people providing 117 diabetic and 130 control subjects. We screened the apolipoprotein A-II gene by single strand conformation polymorphism analysis and fluorescent sequence analysis. Variants were typed by oligonucleotide ligation assay, restriction digest of amplification products, or radioactive fragment analysis for the microsatellite polymorphism. Association of each variant with Type II diabetes was tested in the case-control population by chi-square analysis, or using transmission disequilibrium test in families. Haplotypes were established in families using SIMWALK and tested for association with diabetes and quantitative traits.Results. No detected variant altered the coding sequence of the gene. Three single nucleotide polymorphisms showed modest evidence for an association, but no variant or haplotype was associated with diabetes in families. Similarly, we found no association with non-esterified fatty acid concentrations, HDL concentrations, or fasting insulin. In contrast, we found evidence for an association of some haplotypes and individual variants with 2-h post-challenge glucose and measures of insulin secretion. Conclusion/interpretation. Apolipoprotein

show abstract

“…To obtain high efficiency in linkage analysis, several markers are necessary. However, some DNA polymorphic sites show strong linkage disequilibria (Antonarakis et al, 1982;Chakravarti et al, 1986), reducing their usefulness. Therefore, two or more markers sometimes give essentially the same results.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of Duchenne and Becker muscular dystrophies by DNA polymorphism

et al. 1987

View full text Add to dashboard Cite

SummaryTwenty families affected with Duchenne (DMD) or Becket (BMD) muscular dystrophy from the Japanese population were investigated using six DNA polymorphisms at the pERT87 locus. Allele frequencies for these polymorphisms were different from those found in Caucasians and 94~ of unrelated women were informative for linkage analysis. DMD and BMD phenotypes cosegregated with a particular allele in each family with no obligate recombinants among 50 meiotic events. Among 20 unrelated affected males, one boy had a deletion of at least 52 kilobases (kb) surrounding the pERT87 region.

show abstract

Evidence for increased recombination near the human insulin gene: implication for disease association studies.

Abstract: Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq

Cited by 87 publications

References 32 publications

Multiple restriction fragment length polymorphisms at the insulin receptor locus: a highly informative marker for linkage analysis.

Multiple restriction fragment length polymorphisms at the insulin receptor locus: a highly informative marker for linkage analysis.

Evaluation of apolipoprotein A-II as a positional candidate gene for familial Type II diabetes, altered lipid concentrations, and insulin resistance

Diagnosis of Duchenne and Becker muscular dystrophies by DNA polymorphism

Contact Info

Product

Resources

About