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K Ray

Publications and source records attributed to K Ray.

209 records · Page 12Linked to original sources
PubMedDate not supplied

Strategies for identification of mutations causing hereditary retinal diseases in dogs: evaluation of opsin as a candidate gene.

Progressive retinal atrophy (PRA), like retinitis pigmentosa (RP) in man, represents a clinical classification grouping together a variety of hereditary diseases of the visual cells which have broadly similar clinical characteristics. At least six distinct autosomal recessive and one X-linked retinal disease locus have been identified. As one of the strategies to look for the gene defect causing the different forms of PRA, we are examining first the most promising candidate genes. These include those coding for photoreceptor-specific structural proteins and enzymes of the phototransduction pathway, especially those reported to cause RP. Preeminent among these candidates is the gene for rod opsin, in which multiple causative mutations have been identified in both dominant and recessive forms of RP. In addition, mutations in this gene are also causally associated with congenital stationary night blindness (CSNB) in man. We have used two strategies to examine the rod opsin gene for association with inherited retinal disease in dogs: (1) linkage to determine cosegregation of the disease locus with an intragenic polymorphic marker in the opsin gene in those breeds where suitable informative pedigrees were available; and (2) scanning the coding sequence of the gene in cases where only a limited number of affected or obligate heterozygous samples were available for a breed. We conclude that mutations in the rod opsin gene are not associated with PRA or CSNB in the 11 different dog breeds tested.

Animals↗
PubMedDate not supplied

Frequency of the codon 807 mutation in the cGMP phosphodiesterase beta-subunit gene in Irish setters and other dog breeds with hereditary retinal degeneration.

Rod-cone dysplasia 1 (rcd1) in Irish setters is caused by a nonsense mutation in the cGMP phosphodiesterase beta-subunit gene (PDE6B). We examined the frequency of the mutant allele in the Irish setter population and determined if the defect is present in dogs of other breeds which are affected with other inherited photoreceptor diseases. Between 1994 and 1997, samples were obtained from 436 clinically normal Irish setters, a red wolf, and dogs from 23 different breeds. The mutation in codon 807 of PDE6B was detected in genomic DNA by heteroduplex analysis, allele-specific PCR, or restriction enzyme digestion. Of the 436 samples from clinically normal setters, 34 contained the mutation in one of the two PDE6B alleles (carrier rate = 7.8%). In contrast, the same mutation was not found in the red wolf or dogs of other breeds affected with PRA or inherited photoreceptor diseases. The high percentage of tested carriers, however, is not representative of the number of carriers in the population since some dogs tested were closely related and did not represent a random sample of the Irish setter breed.

3',5'-Cyclic-GMP Phosphodiesterases↗
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Photoreceptor dysplasia (pd) in miniature schnauzer dogs: evaluation of candidate genes by molecular genetic analysis.

Photoreceptor dysplasia (pd) is one of a group of at least six distinct autosomal and one X-linked retinal disorders identified in dogs which are collectively known as progressive retinal atrophy (PRA). It is an early onset retinal disease identified in miniature schnauzer dogs, and pedigree analysis and breeding studies have established autosomal recessive inheritance of the disease. Using a gene-based approach, a number of retina-expressed genes, including some members of the phototransduction pathway, have been causally implicated in retinal diseases of humans and other animals. Here we examined seven such potential candidate genes (opsin, RDS/peripherin, ROM1, rod cGMP-gated cation channel alpha-subunit, and three subunits of transducin) for their causal association with the pd locus by testing segregation of intragenic markers with the disease locus, or, in the absence of informative polymorphisms, sequencing of the coding regions of the genes. Based on these results, we have conclusively excluded four photoreceptor-specific genes as candidates for pd by linkage analysis. For three other photoreceptor-specific genes, we did not find any mutation in the coding sequences of the genes and have excluded them provisionally. Formal exclusion would require investigation of the levels of expression of the candidate genes in pd-affected dogs relative to age-matched controls. At present we are building suitable informative pedigrees for the disease locus with a sufficient number of meiosis to be useful for genomewide screening. This should identify markers linked to the disease locus and eventually permit progress toward the identification of the photoreceptor dysplasia gene and the disease-causing mutation.

Animals↗
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Toward a framework linkage map of the canine genome.

Selective breeding to maintain specific physical and behavioral traits has made the modern dog one of the most physically diverse species on earth. One unfortunate consequence of the common breeding practices used to develop lines of dogs with the desired traits is amplification and propagation of genetic diseases within distinct breeds. To map disease loci we have constructed a first-generation framework map of the canine genome. We developed large numbers of highly polymorphic markers, constructed a panel of canine-rodent hybrid cell lines, and assigned those markers to chromosome groups using the hybrid cell lines. Finally, we determined the order and spacing of markers on individual canine chromosomes by linkage analysis using a reference panel of 17 outbred pedigrees. This article describes approaches and strategies to accomplish these goals.

Animals↗
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Individual DNA bands obtained by RAPD analysis of canine genomic DNA often contain multiple DNA sequences.

The random amplified polymorphic DNA (RAPD) technique has been widely applied for genetic studies of plants, insects, and fungi, and recently has been used for studies in animals including dogs. To convert the RAPD marker into a classical PCR marker, the RAPD-PCR products are size-separated in an agarose gel and a specific DNA band is selected for potential association with a trait of interest. The DNA fragments present in the desired band are then cloned and sequenced using primers specific to the cloning vector, and the sequence is used to design a pair of classical PCR primers. Often a "positive clone" is identified based solely on a match of the size of the insert in the clone with the uncharacterized DNA band originally selected. We observed that single DNA bands obtained from RAPD-PCR using canine genomic DNA often contain DNA fragments of similar size but of different sequences. Based on this observation, we report here a modification of the protocol for RAPD analysis which will ensure that a promising RAPD marker selected based on initial screening is not lost for lack of a comprehensive investigation in the later experimental analysis.

Animals↗
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Increasing trend of HIV seropositivity in a sexually transmitted diseases centre and epidemiology of HIV seropositive individuals.

11,539 STD clinic attenders and 20,897 antenatal clinic (ANC) attenders at a New Delhi hospital were screened for HIV antibodies by ELISA over a 3-year period. Results were confirmed by Western Blot. A low HIV seropositivity rate (1 per 1000) with an increasing trend in 1993 (4 per 1000) was observed in the STD attenders as against 0.1 per 1000 in the normal control populations. Most of the STD attenders including all the HIV seropositives had heterosexual contact with female sex workers. Both the HIV seropositive ANC attenders acquired the infection through blood transfusion. Thirteen of 23 HIV positive STD attenders had genital lesions, 5 having ulcerative and 8 having nonulcerative STD. Their clinical presentation did not differ from the HIV negative cases but the therapeutic response in 4 was altered. None had signs of symptoms of ARC/AIDS. Two out of 6 spouses and a 2-year-old child of HIV seropositive patients were seropositive. Increasing HIV seropositivity observed in this study reflects the changing situation in the country and highlights the importance of improvement of surveillance, early diagnosis and combined approaches to the management and control of STDs and HIV.

Adult↗
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Cholesterol screening in a community health promotion program: epidemiologic results from a biracial population.

The prevalence and interrelationship of high blood cholesterol levels with other cardiovascular disease risk factors were studied in a biracial suburb of New York City. Participants in community-based screenings to determine blood cholesterol levels have been predominantly white women in older age groups, highly educated and nonsmokers. To reach a more representative segment of a local population and promote healthy lifestyle behaviors, cholesterol screenings were conducted within an ongoing health promotion program in Mount Vernon, NY. Plasma cholesterol levels were determined for 5,011 participants, including 2,308 whites and 1,778 blacks. Of the men, 29 percent had high cholesterol levels; among women, it was 27 percent. Of the men with high levels, half had levels greater than 200 milligrams per deciliter, as did 55 percent of the women. After statistical adjustments were made for age and other risk factors for high blood cholesterol, mean cholesterol levels were higher for whites than blacks. The level for white men was 204 milligrams per deciliter; for women, 212. For black men, the level was 199 milligrams per deciliter; for women, 208, P < .10. Hispanic men had levels of 199, P < .10. The levels for Hispanic women (203 milligrams per deciliter) were significantly lower than that of white women. Among whites who smoked more than 1 pack of cigarettes per day, mean cholesterol levels were 11 milligrams per deciliter higher than for those who never smoked or were light smokers (0, 1-20 cigarettes per day, P < .10). There were too few who smoked more than 1 pack to test this association adequately among blacks. The mean cholesterol levels for hypertensive black men were 10 milligrams per deciliter greater than for black men with normal blood pressure (P<.10).

Adult↗