Biomedical subjects

K Chorney

Publications and source records attributed to K Chorney.

7 recordsLinked to original sources

PubMed1999

DNA pooling and dense marker maps: a systematic search for genes for cognitive ability.

Pooling DNA from subjects within a group and comparing the pooled DNA across groups for a dense map of DNA markers offers a solution to the conundrum that linkage is systematic but not powerful whereas allelic association is powerful but not systematic. We used DNA pooling to screen 66 markers on chromosome 22 in original and replication samples of children of high general cognitive ability (g) and controls of average g. Although none of these markers survived our three-stage screening design (original pooling, replication pooling, individual genotyping), the results of DNA pooling were largely confirmed by individual genotyping. We can therefore exclude associations of major effect size on chromosome 22 for g, a key variable for cognitive neuroscience research on learning and memory.

Alleles↗

PubMed1999

DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in children.

General cognitive ability (g), which is related to many aspects of brain functioning, is one of the most heritable traits in neuroscience. Similarly to other heritable quantitatively distributed traits, genetic influence on g is likely to be due to the combined action of many genes of small effect [quantitative trait loci (QTLs)], perhaps several on each chromosome. We used DNA pooling for the first time to search a chromosome systematically with a dense map of DNA markers for allelic associations with g. We screened 147 markers on chromosome 4 such that 85% of the chromosome were estimated to be within 1 cM of a marker. Comparing pooled DNA from 51 children of high g and from 51 controls of average g, 11 significant QTL associations emerged. The association with three of these 11 markers ( D4S2943, MSX1 and D4S1607 ) replicated using DNA pooling in independent samples of 50 children of extremely high g and 50 controls. Furthermore, all three associations were confirmed when each individual was genotyped separately ( D4S2943, P = 0. 00045; MSX1, P = 0.011; D4S1607, P = 0.019). Identifying specific genes responsible for such QTL associations will open new windows in cognitive neuroscience through which to observe pathways between genes and learning and memory.

Adolescent↗

PubMed1998

Dopamine markers and general cognitive ability.

Because general cognitive ability (g) is among the most heritable behavioural traits, it is a reasonable target for a search for quantitative trait loci (QTLs). We used a selected-extremes design to test candidate genes for allelic association with g. Polymorphisms in four genes in the dopamine system (DRD2, DRD3, DRD4, DAT1) were genotyped for 51 high g children with IQ scores > 130 and for 51 average g control children. No significant allelic or genotypic differences were found between the high g and average g groups for these markers of the dopamine system, even though the selected-extremes design provides power to detect QTL associations that involve a relative risk of about 1.5.

Adolescent↗

PubMed1997

Chronic pain following ankle sprains in athletes: the role of arthroscopic surgery.

We reviewed 100 patients treated arthroscopically for symptoms of chronic ankle pain associated with sprains of the ankle. All had pain that had failed to respond to conservative treatment for at least 6 months. The pathology in 95 of the 100 ankles studied could be categorized into one of three groups: the instabilities (lateral and syndesmotic), the impingements (anterior and anterolateral), and articular lesions (chondral and osteochondral). Five patients had nonspecific osteoarthritis and/or synovitis on arthroscopy. Patients were followed-up for improvements in six categories: pain, swelling, stiffness, limping, activity, and instability. The primary outcomes of pain and activity were analyzed statistically. Patient satisfaction and return to sports were evaluated. Significant improvements were obtained for patients treated for syndesmotic instability, and anterior and anterolateral impingement. Chondral fractures in the presence of a stable ankle had good results in 75% of cases, compared with those in unstable ankles with only 33% good results. Osteochondritis dissecans was treated successfully by excision of the lesion and abrasion of the base. Patients with chronic lateral instability were treated by open repair, so only the diagnostic arthroscopic findings are reported. We concluded that arthroscopy offered little to the management of lateral instability unless there was considerable doubt regarding the diagnosis. There were minimal improvements for the patients with nonspecific diagnoses such as posttraumatic synovitis. Ankle arthroscopy may be a very useful diagnostic and therapeutic tool in patients who have not responded to conservative therapy.

Ankle Injuries↗

PubMed1997

No association between general cognitive ability and the A1 allele of the D2 dopamine receptor gene.

Berman and Noble (1995) reported significantly reduced visuospatial performance in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene. Given that visuospatial performance loads highly on an unrotated principal component indexing general cognitive ability, we tested the association between DRD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in the IQ Quantitative Trait Loci (QTL) Project. No statistically significant association between the TAQI A DRD2 alleles and IQ was found. Given that a statistically significant portion of genetic variance for specific cognitive abilities is independent of general cognitive ability, it is possible that the TAQI DRD2 association is specific to visuospatial performance and independent of general cognitive ability.

Adolescent↗

PubMed1996

Precise localisation of 3p25 breakpoints in four patients with the 3p-syndrome.

In patients with the 3p-syndrome, hemizygous deletion of 3p25-pter is associated with profound growth failure, characteristic facial features, and mental retardation. We performed a molecular genetic analysis of 3p25 breakpoints in four patients with the 3p- syndrome, and a fifth patient with a more complex abnormality, 46,XY,der(3)t(3;?)(p25.3;?). EBV transformed lymphoblasts from each of the patients were initially characterised using fluorescent in situ hybridisation (FISH) and polymorphic microsatellite analyses. The 3p-chromosome from each patient was isolated from the normal chromosome 3 in somatic cell hybrid lines and subsequently analysed with polymorphic and monomorphic PCR amplifiable markers from 3p25. The analysis clearly shows that all five breakpoints are distinct. Furthermore, we have identified yeast artificial chromosomes that cross the 3p25 breakpoints of all four 3p-patients. Two of the patients were deleted for the von Hippel-Lindau (VHL) tumour suppressor gene, although neither has yet developed evidence of VHL disease. The patient with the most centromeric breakpoint, between D3S1585 and D3S1263, had the most severe clinical phenotype including an endocardial cushion defect that was not observed in any of the four patients who had more telomeric breakpoints. This study should provide useful insights into critical regions within 3p25 that are involved in normal human growth and development.

Abnormalities, Multiple↗

PubMed1994

DNA markers associated with high versus low IQ: the IQ Quantitative Trait Loci (QTL) Project.

General cognitive ability (intelligence, often indexed by IQ scores) is one of the most highly heritable behavioral dimensions. In an attempt to identify some of the many genes (quantitative trait loci; QTL) responsible for the substantial heritability of this quantitative trait, the IQ QTL Project uses an allelic association strategy. Allelic frequencies are compared for the high and low extremes of the IQ dimension using DNA markers in or near genes that are likely to be relevant to neural functioning. Permanent cell lines have been established for low-IQ (mean IQ = 82; N = 18), middle-IQ (mean IQ = 105; N = 21), and high-IQ (mean IQ = 130; N = 24) groups and for a replication sample consisting of even more extreme low-IQ (mean IQ = 59; N = 17) and high-IQ (mean IQ = 142; N = 27) groups. Subjects are Caucasian children tested from 6 to 12 years of age. This first report of the IQ QTL Project presents allelic association results for 46 two-allele markers and for 26 comparisons for 14 multiple-allele markers. Two markers yielded significant (p < .01) allelic frequency differences between the high- and the low-IQ groups in the combined sample-a new HLA marker for a gene unique to the human species and a new brain-expressed triplet repeat marker (CTGB33). The prospects for harnessing the power of molecular genetic techniques to identify QTL for quantitative dimensions of human behavior are discussed.

Alleles↗