Microsatellite genotyping of Chromosome 14q13.2-14q13 in the vicinity of proteasomal gene PSMA6 and association with Graves? disease in the Latvian population

Abstract

The 270-kb chromosome 14q13.2-14q13 region harboring the proteasomal alpha subunit 6 gene PSMA6 was analyzed for polymorphism of five microsatellite repeats in cases/controls and association with Graves' disease. Four novel microsatellite markers were localized to the 14q13.2 region upstream of PSMA6. Dinucleotide repeats HSMS801, HSMS702, HSMS701 were identified in two introns of the gene KIAA0391; the most upstream trinucleotide HSMS602 marker was found in an intron of the C14orf24 gene. A polymorphism study performed on the Latvian population revealed 13 and 14 alleles for HSMS801 and HSMS702, respectively, seven alleles for HSMS701, and four alleles for HSMS602. Heterozygosity analysis revealed that all the four markers obey Hardy-Weinberg distribution. The previously described HSMS006 marker, represented by 12 alleles, is localized in intron 6 of the PSMA6 gene. No significant differences were observed between patients and controls in allele distribution of the HSMS702 and HSMS701 microsatellite repeats. However, the allele frequencies of HSMS006 and HSMS801 were significantly different between Graves' disease and control subjects. The 181- and 185-bp alleles of HSMS006 and the 133-, 143-, and 149-bp alleles of HSMS801 were found more often, but the 189- and 191-bp alleles of HSMS006 were much less frequent in Graves' disease patients compared with the controls. An additional 174-bp allele of the HSMS602 marker, absent in healthy subjects, was found in Graves' disease patients.

Absence of mutations in Pax6 gene in three cases of Morning Glory syndrome associated with isolated growth hormone deficiency

“…To support this idea, there is the fi nding that a variable number of TG repeats present in intron 8 of CFTR gene contributes to phenotype diversity in Cystic Fibrosis by forming RNA secondary structures that alter exon 9 splicing process (21). Linkages of TG repeats within intronic regions of different genes, including PAX7 which belongs to the same PAX6 gene family, have been described in a few diseases (22)(23)(24). Therefore, it is possible that nucleotide alterations within introns might have effects in transcript productions.…”

“…Normally, PAX6 alleles bear a sequence of (TG) [19][20][21][22][23][24][25][26][27][28][29] repeats interrupted by a GG dinucleotide and followed by a (TG) 7 repeat. Patients A and C were heterozygous for (TG) 19/21 -GG -(TG) 7 sequences, however patient B was heterozygous for (TG) 16/19 repeats with absence of the intercalated GG dinucleotide and the last (TG) 7 repeats (Table 3).…”

Identification of a Novel Candidate Locus for Juvenile Idiopathic Arthritis at 14q13.2 in the Latvian Population by Association Analysis with Microsatellite Markers

“…To improve the reliability of our data, formerly based mostly on fragment size analysis (Sjakste et al, 2004(Sjakste et al, , 2007, we have checked the MS motifs by sequencing. Genomic regions encompassing MS repeats were amplified and sequenced in several specimens to annotate the MS length variability to MS repeat number variation.…”

“…Information on the markers used, genes nesting MS, and loci polymorphism are summarized in Table 2. Polymerase chain reaction products for MS fragment sizing were amplified with HSMS primers as previously described (Sjakste et al, 2002(Sjakste et al, , 2004(Sjakste et al, , 2007. DNA fragments were separated by capillary electrophoresis using the ABI Prism Ò 310 Genetic Analyzer (Applied Biosystems, Foster, CA).…”

“…A chromosome 14q screen with 14 microsatellite (MS) markers revealed evidence for genetic linkage between immunoglobulin E phenotypes and 14q11.2 and 14q13-23 loci (Mansur et al, 1999). Fine genotyping of the 14q13.2 region encompassing FAM177A1, KIAA0391, and PSMA6 genes by five intronic MS revealed association of several alleles and genotypes with Graves' disease (Sjakste et al, 2004). Evidence for linkage between the 14q13-23 region and susceptibility for rheumatoid arthritis resulted from the rheumatoid arthritis genome scan performed with 309 markers outside the HLA region (Cornélis et al, 1998).…”