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- Alkayyali, Sami, et al.
(författare)
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Genetics of diabetes complications.
- 2014
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Ingår i: Mammalian Genome. - : Springer Science and Business Media LLC. - 1432-1777 .- 0938-8990. ; 25:9-10, s. 384-400
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Tidskriftsartikel (refereegranskat)abstract
- Chronic hyperglycemia and duration of diabetes are the major risk factors associated with development of micro- and macrovascular complications of diabetes. Although it is believed that hyperglycemia induces damage to the particular cell subtypes, e.g., mesangial cells in the renal glomerulus, capillary endothelial cells in the retina, and neurons and Schwann cells in peripheral nerves, the exact mechanisms underlying these damaging defects are not yet well understood. Clustering of micro- and macrovascular complications in families of patients with diabetes suggests a strong genetic susceptibility. However, until now only a handful number of genetic variants were reported to be associated with either nephropathy (ACE, ELMO1, FRMD3, and AKR1B1) or retinopathy (VEGF, AKR1B1, and EPO), and only a few studies were carried out for genetic susceptibility to cardiovascular diseases (ADIPOQ, GLUL) in patients with diabetes. It is, therefore, obvious that the accumulation of more data from larger studies and better phenotypically characterized cohorts is needed to facilitate genetic discoveries and unravel novel insights into the pathogenesis of diabetic complications.
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| 2. |
- Andersson, Lisa, et al.
(författare)
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Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases
- 2011
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Ingår i: Mammalian Genome. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 22, s. 353-360
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Tidskriftsartikel (refereegranskat)abstract
- The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4, were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17, the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain.
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| 3. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human.
- 2002
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Ingår i: Mammalian genome : official journal of the International Mammalian Genome Society. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 13:6, s. 302-9
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Tidskriftsartikel (refereegranskat)abstract
- The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related ( Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.
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| 4. |
- Belknap, J K, et al.
(författare)
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The replicability of QTLs for murine alcohol preference drinking behavior across eight independent studies.
- 2001
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Ingår i: Mammalian Genome. - New York : Springer-Verlag New York. - 0938-8990 .- 1432-1777. ; 12:12, s. 893-899
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Tidskriftsartikel (refereegranskat)abstract
- On the basis of eight independent quantitative trait loci (QTL) studies of ethanol (alcohol) preference drinking in mice, a meta-analysis was carried out to examine the replicability of QTLs across studies and to enhance the power of QTL detection and parameter estimation. To avoid genetic heterogeneity, we analyzed only studies of mapping populations derived from the C57BL/6 (B6) and DBA/2 (D2) inbred progenitor strains. Because these studies were carried out in five different laboratories, there were substantial differences in testing procedure, data analysis, and especially in the choice of mapping population (BXD recombinant inbred strains, F2, backcross, selected lines, or congenic strains). Despite this, we found several QTLs that were sufficiently robust as to appear consistently across studies given the strengths and weaknesses of the mapping populations employed. These were on Chromosomes (Chrs) 2 (proximal to mid), 3 (mid to distal), 4 (distal), and 9 (proximal to mid). The P value for each of these QTLs, combined across all applicable studies, ranged from 10(-7) to 10(-15), with the additive effect of each QTL accounting for 3-5% of the trait variance extrapolated to an F2 population. Two other QTLs on Chrs 1 (distal) and 11 (mid) were less consistent, but still reached overall significance (P <.0001).
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| 6. |
- Carlborg, Örjan, et al.
(författare)
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Simultaneous mapping of epistatic QTL in DU6i x DBA/2 mice.
- 2005
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Ingår i: Mammalian Genome. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 16:7
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Tidskriftsartikel (refereegranskat)abstract
- We have mapped epistatic quantitative trait loci (QTL) in an F2 cross between DU6i x DBA/2 mice. By including these epistatic QTL and their interaction parameters in the genetic model, we were able to increase the genetic variance explained substantially (8.8%-128.3%) for several growth and body composition traits. We used an analysis method based on a simultaneous search for epistatic QTL pairs without assuming that the QTL had any effect individually. We were able to detect several QTL that could not be detected in a search for marginal QTL effects because the epistasis cancelled out the individual effects of the QTL. In total, 23 genomic regions were found to contain QTL affecting one or several of the traits and eight of these QTL did not have significant individual effects. We identified 44 QTL pairs with significant effects on the traits, and, for 28 of the pairs, an epistatic QTL model fit the data significantly better than a model without interactions. The epistatic pairs were classified by the significance of the epistatic parameters in the genetic model, and visual inspection of the two-locus genotype means identified six types of related genotype-phenotype patterns among the pairs. Five of these patterns resembled previously published patterns of QTL interactions.
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