Mapping of the OB receptor to 1p in a region of nonconserved gene order from mouse and rat to human.

Chung, Wendy K.; Power-Kehoe, Loraine; Chua, Melvin L.K.; Leibel, Rudolph L.

doi:10.1101/gr.6.5.431

Cited by 55 publications

(30 citation statements)

References 34 publications

(16 reference statements)

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“…16 The human leptin receptor LEPR gene 22 maps to 1p31-p22. 23 No linkage was observed between markers in the vicinity of LEPR and obesity in Pima Indians, 24 ± 26 as in a French population, 27 whereas suggestive linkages were reported in the Que Âbec Family Study (QFS). 28 Some 18 different polymorphisms in the human LEPR gene have been reported (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Québec Family Study

et al. 1999

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OBJECTIVE: To investigate linkage and association between the leptin receptor (LEPR) gene and body composition variables in the Que Â bec Family Study (QFS). DESIGN: Single-point linkage analysis using families, and covariance and chi-square analyses using normal weight and obese unrelated subjects from QFS. SUBJECTS: 169 nuclear families were used for linkage study. 308 unrelated subjects (146 males; 162 females) from these families were used for chi-square testing of genotype and allele distributions between subjects with body mass index (BMI)`27 kgam 2 (n 167) and those with BMI ! 27 kgam 2 (n 141), and for a series of covariance analyses using age, plus height for fat mass (FM) and fat free mass (FFM), as covariates. A corrected P value (P*) for multiple tests has been calculated according to P* 1-(1-P) number of phenotypes . MEASUREMENTS: Variables were BMI (in kgam 2 ), sum of six skinfolds (SF6 in mm), FM (in kg), percent body fat (%FAT) and FFM (in kg). Polymerase chain react restricted fragment length polymorphisms PCR-RFLP) was used to identi®ed a K109R substitution in exon 4, a Q223R in exon 6, a K656N in exon 14 and an automatic DNA sequencer for a CA microsatellite repeat in intron 3, and heteroduplex pattern on non-denaturing gel for a CTTT repeat in intron 16. RESULTS: Good evidence of linkage was observed for Q223R with FM (P 0.005; P* 0.02), and for the CTTT repeat with FFM (P 0.007; P* 0.03). Weaker linkages (0.02 P 0.05) were also observed between Q223R and BMI, SF6 and FFM, between the CA repeat and BMI, SF6 and FM, and between the CTTT repeat and FM. Moreover, FFM values were found to be different among genotypes for the CTTT repeat polymorphism with heavier females, carriers of the 123* allele at the CTTT repeat, showing 4 kg less of FFM (43.6 AE 1.0, n 21 vs 47.7 AE 0.8, n 30; P 0.005; P* 0.02) than non-carriers. Also, at the Q223R polymorphism, in lower BMI males, carriers of the Q223 allele were 4 kg lighter in FFM (53.4 AE 0.6, n 47 vs 56.6 AE 0.9, n 18; P 0.005; P* 0.02) than non-carriers. No signi®cant differences were observed between lower and higher BMI subjects in genotype and allele frequency distributions for any of the polymorphisms. CONCLUSIONS: These results indicate that the LEPR gene is involved in the regulation of the body composition in human particularly of FFM in the QFS.

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Section: Introductionmentioning

confidence: 99%

Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Québec Family Study

et al. 1999

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“…The linkage of obesity-related phenotypes in humans to genomic regions homologous to rodent leptin (Lep) (3) and leptin receptor (Lepr) (4,5) has been recently demonstrated. The recent cloning of Lepr, which is mutant in the diabetes (Lepr^) mouse and in fatty (Lepr fa ) and Koletsky (Lepr fqf ) rats (6-9), the mapping of this gene (LEPR) to Ip32 in humans (10), and the description of the genomic structure of LEPR and two polymorphic intronic microsatellites (11) have provided the necessary reagents for the evaluation of LEPR in the genetics of human obesity.…”

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confidence: 99%

Exonic and Intronic Sequence Variation in the Human Leptin Receptor Gene (LEPR)

et al. 1997

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“…In the case of intragenic markers HOB, OBR-CTTT and OBR-CA, the PCR primers were as suggested. 30,31 Radiation hybrid mapping 32 was carried out using the Stanford G3 Radiation Hybrid Panel (Research Genetics, Huntsville, AL, USA) to clarify the interrelation of polymorphic markers and the MC4-R gene. The PCRs were carried out with 15-25 µg of DNA in a reaction volume of 15-25 µl using MJ Research thermal cycler.…”

Section: Genotypingmentioning

confidence: 99%

Testing of human homologues of murine obesity genes as candidate regions in Finnish obese sib pairs

et al. 1999

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The human homologues of recently discovered murine obesity genes provide relevant candidates to study the genetic component of obesity in humans. We analysed the human counterparts to murine obesity genes ob, db, agouti, tub, melanocortin 4-receptor (MC4-R) and mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3), as well as two other chromosomal regions reported to be linked to obesity-related phenotypes in restricted populations. We found no significant evidence for linkage to any analysed loci in our total study material of 105 affected sib pairs collected from the genetically homogenous population of Finland. However, several markers on 14 cM chromosomal region flanking the MC4-R gene showed sharing of alleles identical-by-descent (IBD) more frequently than expected. A selected subset of non-diabetic obese sib pairs strengthened the P values down to 0.003 in this particular region. The smallest P value (P = 0.001) was obtained with a marker D18S487 in a subgroup containing only sib pairs with one lean and one obese parent. We therefore screened seven obese subjects included in our sib pair material for sequence changes in their MC4-R gene, but no mutations of apparent causal relationship were found. In conclusion, we could not find evidence for significant contribution of the chromosomal loci corresponding to the murine single gene obesity genes for human morbid obesity, but additional studies are still needed to clarify whether DNA alterations within or adjacent to the MC4-R gene play some role.

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Mapping of the OB receptor to 1p in a region of nonconserved gene order from mouse and rat to human.

Cited by 55 publications

References 34 publications

Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Québec Family Study

Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Québec Family Study

Exonic and Intronic Sequence Variation in the Human Leptin Receptor Gene (LEPR)

Testing of human homologues of murine obesity genes as candidate regions in Finnish obese sib pairs

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