Analysis Of Genotype Distribution Research Articles

Inactivation of NuRD Component Mta2 Causes Abnormal T Cell Activation and Lupus-like Autoimmune Disease in Mice

Dynamic changes in chromatin structure through ATP-dependent remodeling and covalent modifications on histones play important roles in transcription regulation. Among the many chromatin modifiers identified, the NuRD (nucleosome remodeling histone deacetylase) complex is unique because it possesses both nucleosome remodeling and histone deacetylase activities. To understand the biological function of the NuRD complex, we generated a knock-out mouse model of the Mta2 (metastasis-associated protein 2) gene, which encodes a NuRD-specific component. Mta2 null mice exhibited partial embryonic lethality. The surviving mice developed lupus-like autoimmune symptoms including skin lesions, bodyweight loss, glomerulonephritis, liver inflammation, and production of autoantibodies. Transplantation of bone marrow cells from Mta2 null mice recapitulated some of the symptoms including skin lesion and bodyweight loss in the recipient mice. Mta2 null T lymphocytes showed normal development but hyperproliferation upon stimulation, which correlates with hyperinduction of interleukin (IL)-2, IL-4, and interferon (IFN)-gamma. T cell hyperproliferation, but not other autoimmune symptoms, was observed in T cell-specific Mta2 knock-out mice. Mta2 null T cells produced more IL-4 and IFN-gamma under Th2 activation conditions, but normal levels of IL-4 and IFN-gamma under Th1 activation conditions. Furthermore, we found that IL-4 is a direct target gene of Mta2. Our study suggests that Mta2/NuRD is involved in modulating IL-4 and IFN-gamma expression in T cell immune responses, and gene expression in non-T cells plays an important role in controlling autoimmunity.

Genetic analysis of the breeding system of an invasive subterranean termite, Reticulitermes santonensis, in urban and natural habitats

Reticulitermes santonensis is a subterranean termite that invades urban areas in France and elsewhere where it causes damage to human-built structures. We investigated the breeding system, colony and population genetic structure, and mode of dispersal of two French populations of R. santonensis. Termite workers were sampled from 43 and 31 collection points, respectively, from a natural population in west-central France (in and around the island of Oleron) and an urban population (Paris). Ten to 20 workers per collection point were genotyped at nine variable microsatellite loci to determine colony identity and to infer colony breeding structure. There was a total of 26 colonies, some of which were spatially expansive, extending up to 320 linear metres. Altogether, the analysis of genotype distribution, F-statistics and relatedness coefficients suggested that all colonies were extended families headed by numerous neotenics (nonwinged precocious reproductives) probably descended from pairs of primary (winged) reproductives. Isolation by distance among collection points within two large colonies from both populations suggested spatially separated reproductive centres with restricted movement of workers and neotenics. There was a moderate level of genetic differentiation (F(ST) = 0.10) between the Oleron and Paris populations, and the number of alleles was significantly higher in Oleron than in Paris, as expected if the Paris population went through bottlenecks when it was introduced from western France. We hypothesize that the diverse and flexible breeding systems found in subterranean termites pre-adapt them to invade new or marginal habitats. Considering that R. santonensis may be an introduced population of the North American species R. flavipes, a breeding system consisting primarily of extended family colonies containing many neotenic reproductives may facilitate human-mediated spread and establishment of R. santonensis in urban areas with harsh climates.

Hepatic cholangiodysplastic pseudocirrhosis with multiple disseminated intrahepatic nodules of pancreatic tissue

We developed an inbred rat model of diabetic embryopathy, in which the offspring displays skeletal malformations (agnathia or micrognathia) when the mother is diabetic, and no malformations when she is not diabetic. Our aim was to find genes controlling the embryonic maldevelopment in a diabetic environment.We contrasted the fetal outcome in inbred Sprague-Dawley L rats (20% skeletal malformations in diabetic pregnancy) with that of inbred Wistar Furth rats (denoted W, no skeletal malformations in diabetic pregnancy). We used offspring from the backcross F1 × L to probe for the genetic basis for malformation of the mandible in diabetic pregnancy. A set of 186 fetuses (93 affected, 93 unaffected) was subjected to a whole genome scan with 160 micro satellites. Analysis of genotype distribution indicated 7 loci on chromosome 4, 10 (3 loci), 14, 18, and 19 in the teratogenic process (and 14 other loci on 12 chromosomes with less strong association to the malformations), several of which contained genes implicated in other experimental studies of diabetic embryopathy. These candidate genes will be scrutinized in further experimentation.We conclude that the genetic involvement in rodent diabetic embryopathy is polygenic and predisposing for congenital malformations.

Possible association of temporomandibular joint pain and dysfunction with a polymorphism in the serotonin transporter gene.

The purpose of this study was to evaluate the relationship between temporomandibular joint pain and dysfunction and serotonin transporter (5-HTT) gene polymorphism. Forty-eight patients with temporomandibular joint pain and 111 healthy control subjects were examined. The results for the patients and control subjects were not significantly different (P >.05). The analysis of genotype distribution (homozygous for STin 2.10 genotypes of the variable-number tandem-repeat polymorphism) showed significant differences between the patients and control subjects (P =.003). ST 2.10 allele was more frequent in the patients with temporomandibular joint pain and dysfunction. In the control group, however, STin 2.12/12 genotype was significantly higher (P =.017). In the patients who were homozygous or heterozygous for variable-number tandem-repeat variants of 5-HTT STin 2.12 copies, the average scores of somatization and anger were significantly higher than those who were homozygous for STin 2.10 variant (P <.05). The patients who were homozygous for STin 2.10 genotype were also homozygous for "L" genotype (P =.019). However, this was not the condition in the control subjects. This study does not provide evidence to support the involvement of 5-HTT gene-linked polymorphic region in temporomandibular joint pain and dysfunction. Our findings indicated that only the presence of the homozygous STin 2.10 genotype of variable-number tandem-repeat is likely to play a substantial role in the genetic predisposition to temporomandibular joint pain and dysfunction and that the STin 2.12/12 genotype may have a protective role against temporomandibular joint pain and dysfunction.

Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease.

Cytokine gene variations are contributory factors in inflammatory pathology. Allele frequencies of interleukin (IL)-1 cluster genes [IL-1A(-889), IL-1B(-511), IL-1B(+3953), IL-1RN Intron 2 VNTR] and tissue necrosis factor (TNF)-alpha gene [TNFA(-308)] were measured in healthy blood donors (healthy control subjects), patients with angiographically normal coronary arteries (patient control subjects), single-vessel coronary disease (SVD), and those with multivessel coronary disease (MVD). Five hundred fifty-six patients attending for coronary angiography in Sheffield were studied: 130 patient control subjects, 98 SVD, and 328 MVD. Significant associations were tested in an independent population (London) of 350: 57 SVD, 191 MVD, and 102 control subjects. IL-1RN*2 frequency in Sheffield patient control subjects was the same as in 827 healthy control subjects. IL-1RN*2 was significantly overrepresented in Sheffield SVD patients (34% vs 23% in patient control subjects); IL-1RN*2 homozygotes in the SVD population (chi2 carriage=8.490, 1 df, P=0.0036). This effect was present though not quite significant in the London population (P=0. 0603). A summary trend test of the IL-1RN SVD genotype data for Sheffield and London showed a significant association with *2 (P=0. 0024). No significant effect of genotype at IL-1RN was observed in the Sheffield or London MVD populations. Genotype distribution analysis comparing the SVD and MVD populations at IL-1RN showed a highly significant trend (P=0.0007) with the use of pooled data. No significant associations were seen for the other polymorphisms. IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.

Nucleotide sequence of the 1.2-kb 3'-region and genotype distribution of two common c- myc alleles of the domestic cat

Nucleotide (nt) sequence analyses of the 1.2-kb BamHI- EcoRI cloned 3'-fragment encompassing the polymorphic Smal restriction site of the feline c-myc gene reveal that the SmaI site, present in CM2 allele but absent from CM3 allele, is located in intron 2, 134 nt 5' of the exon 3. A G-to-C transversion in CM2 results in the creation of the SmaI site. Additionally, the alleles differ at four other nt positions in intron 2, three of these changes being in a region of the intron which exhibits 80 % homology between the feline and human c- myc. The alleles also differ in two nt positions in exon 3 in the third position of the codon resulting, however, in no amino acid alteration. Genotype distribution analysis based on the SmaI polymorphism shows that CM2 homozygosity is rare and its frequency deviates significantly from the expected distribution patterns for independently segregating alleles.

Verification allelic polymorphism's of genes MTHFR and MTR in patients with psoriasis

Aim. Analysis of single nucleotide polymorphisms C677T, A1298C and A2756G of MTHFR and MTR one-carbon metabolism genes in patients with various forms of psoriasis in Ukrainian population. Methods. A molecular genetic analysis of 77 patients with vulgaris and arthropathic psoriasis by PCR-RFLP was carried out. Results. In patients with vulgaris and arthropathic psoriasis analysis of the distribution of frequencies of genotypes showed a statistically significant difference between them for C677T polymorphic variants. In patients with psoriasis analysis of genotype distribution of series in the two genes as a whole, showed a statistically significant difference between the theoretically expected and actual frequencies for single nucleotide polymorphisms A1298T and A2756G of MTHFR and MTR genes. Conclusions. Among patients with arthropatic psoriasis, which is the most severe form of psoriasis, the homozygotes for the wild-type allele G of A2756G of MTR gene are more rarely, homozygotes of the TT of C667T of MTHFR gene are found more common than among psoriasis vulgaris patients, which may indicate the contribution of other genes to the development of arthropatic psoriasis.&#x0D; Keywords: psoriasis, arthropatic psoriasis, folate cycle, MTHFR gene, MTR gene.