FOXE1 polyalanine tract length screening by MLPA in idiopathic premature ovarian failure

<p>Abstract</p> <p>Background</p> <p>FOXE1 is one of the candidate genes for genetic predisposition to premature ovarian failure (POF) and it contains an alanine tract. Our purpose is to assess the influence of length of the alanine tract of FOXE1 on genetic susceptibility to POF.</p> <p>Methods</p> <p>The group studied consisted of 110 Chinese patients with idiopathic POF and 110 women from normal controls. The polyalanine tract and flanking sequence of FOXE1 was screened using the Multiple Ligation-dependent Probe Amplification (MLPA) technique and directly sequenced.</p> <p>Results</p> <p>Three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. There were significantly lower frequencies of the 14/14 genotypes in cases with POF (X2 = 119.73, P = 0.001), as compared with the controls. The incidence of 16/16 genotypes of FOXE1-polyalanine was significantly higher in patients with POF (X2 = 3.403, P = 0.001) in comparison to the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group (186/220) than the controls (216/220) (X2 = 25.923, P = 0.0001). The FOXE1 16 alanine allele was significantly more common in the POF patient group (28/220) than the controls (4/220) (X2 = 19.412, P = 0.0001).</p> <p>Conclusion</p> <p>This finding provides evidence that polyalanine repeat expansions in FOXE1 may be responsible for the genetic aetiology of POF in Chinese women.</p

Testing and Data Reduction of the Chinese Small Telescope Array (CSTAR) for Dome A, Antarctica

The Chinese Small Telescope ARray (hereinafter CSTAR) is the first Chinese astronomical instrument on the Antarctic ice cap. The low temperature and low pressure testing of the data acquisition system was carried out in a laboratory refrigerator and on the 4500m Pamirs high plateau, respectively. The results from the final four nights of test observations demonstrated that CSTAR was ready for operation at Dome A, Antarctica. In this paper we present a description of CSTAR and the performance derived from the test observations.Comment: Accepted Research in Astronomy and Astrophysics (RAA) 1 Latex file and 20 figure

Identification of susceptibility genes in non-syndromic cleft lip with or without cleft palate using whole-exome sequencing

Background: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P. Material and Methods: Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing. Results: By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subsequently compared the SNVs against public databases including NCBI dbSNP build 135 and 1000 Genomes Project and obtained an average of 203 SNVs. Total 12 reported candidate genes were verified by Sanger sequencing. Sanger sequencing also confirmed 16 novel SNVs shared by two or more samples. Conclusions: We have found and confirmed 16 susceptibility genes responsible for NSCL/P, which may play important role in the etiology of NSCL/P. The susceptibility genes identified in this study will not only be useful in revealing the etiology of NSCL/P but also in diagnosis and treatment of the patients with NSCL/P

TMRT observations of 26 pulsars at 8.6 GHz

Integrated pulse profiles at 8.6~GHz obtained with the Shanghai Tian Ma Radio Telescope (TMRT) are presented for a sample of 26 pulsars. Mean flux densities and pulse width parameters of these pulsars are estimated. For eleven pulsars these are the first high-frequency observations and for a further four, our observations have a better signal-to-noise ratio than previous observations. For one (PSR J0742-2822) the 8.6~GHz profiles differs from previously observed profiles. A comparison of 19 profiles with those at other frequencies shows that in nine cases the separation between the outmost leading and trailing components decreases with frequency, roughly in agreement with radius-to-frequency mapping, whereas in the other ten the separation is nearly constant. Different spectral indices of profile components lead to the variation of integrated pulse profile shapes with frequency. In seven pulsars with multi-component profiles, the spectral indices of the central components are steeper than those of the outer components. For the 12 pulsars with multi-component profiles in the high-frequency sample, we estimate the core width using gaussian fitting and discuss the width-period relationship.Comment: 33 pages, 49 figures, 5 Tables; accepted by Ap

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes

BACKGROUND: The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. RESULTS: We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen α1 (COL1A1), estrogen receptor-α (ER-α), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-β1 (TGF-β1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D(3)) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r(2), were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r(2 )was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. CONCLUSION: The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies

Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis

BACKGROUND: Public SNP databases are frequently used to choose SNPs for candidate genes in the association and linkage studies of complex disorders. However, their utility for such studies of diseases with ethnic-dependent background has never been evaluated. RESULTS: To estimate the accuracy and completeness of SNP public databases, we analyzed the allele frequencies of 41 SNPs in 10 candidate genes for obesity and/or osteoporosis in a large American-Caucasian sample (1,873 individuals from 405 nuclear families) by PCR-invader assay. We compared our results with those from the databases and other published studies. Of the 41 SNPs, 8 were monomorphic in our sample. Twelve were reported for the first time for Caucasians and the other 29 SNPs in our sample essentially confirmed the respective allele frequencies for Caucasians in the databases and previous studies. The comparison of our data with other ethnic groups showed significant differentiation between the three major world ethnic groups at some SNPs (Caucasians and Africans differed at 3 of the 18 shared SNPs, and Caucasians and Asians differed at 13 of the 22 shared SNPs). This genetic differentiation may have an important implication for studying the well-known ethnic differences in the prevalence of obesity and osteoporosis, and complex disorders in general. CONCLUSION: A comparative analysis of the SNP data of the candidate genes obtained in the present study, as well as those retrieved from the public domain, suggests that the databases may currently have serious limitations for studying complex disorders with an ethnic-dependent background due to the incomplete and uneven representation of the candidate SNPs in the databases for the major ethnic groups. This conclusion attests to the imperative necessity of large-scale and accurate characterization of these SNPs in different ethnic groups