[Correlation study on 12p13 single nucleotide polymorphism rs12425791 and Chinese medical syndrome types in ischemic stroke patients of the Han nationality].

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Jan;33(1):47-50

Authors: Xie JJ, Gu L, Chen Q, Wu GL, Yan Y, Su L

Abstract
OBJECTIVE: To explore the correlation between 12p13 single nucleotide polymorphism (SNP) rs12425791 and Chinese medical syndrome types of ischemic stroke patients of the Han nationality.
METHODS: A case-control study was used. Recruited were 148 ischemic stroke patients of the Han nationality (67 patients of phlegm syndrome and 81 patients of blood stasis syndrome). Another 192 healthy subjects were recruited as the control group. The genotypes of rs12425791 were performed by TaqMan SNP genotyping assays to analyze the distribution of genes and the distribution frequency of alleles.
RESULTS: There was no statistical difference in the genotype and alleles of rs12425791 between the ischemic stroke patients of phlegm syndrome and the control group, or between the ischemic stroke patients of blood stasis syndrome and the control group (P > 0.05).
CONCLUSION: Our results did not support that 12p13 common variant rs12425791 was correlated with the pathogeneses of ischemic stroke patients of phlegm syndrome and ischemic stroke patients of blood stasis syndrome.

PMID: 23596786 [PubMed - in process]

Shared genetic factors for age at natural menopause in Iranian and European women.

Hum Reprod. 2013 Apr 16;

Authors: Rahmani M, Earp MA, Ramezani Tehrani F, Ataee M, Wu J, Treml M, Nudischer R, P-Behnami S, ReproGen Consortium, Perry JR, Murabito JM, Azizi F, Brooks-Wilson A

Abstract
STUDY QUESTION: Do differences in heritable genetic factors explain some of the difference in age at natural menopause (ANM) among populations? SUMMARY ANSWER: One single nucleotide polymorphism (SNP)-ANM association (rs16991615) detected in European women was replicated in Iranian women. WHAT IS KNOWN ALREADY: Genetics plays an important role in ANM, and well-powered genome-wide association studies (GWAS) of ANM performed in European women have discovered many statistically significant SNP-ANM associations. Average ANM varies by ethnicity, and population-specific differences in ANM-associated alleles may in part explain these differences. STUDY DESIGN, SIZE, DURATION: After quality control procedures, 97 SNPs were analyzed in genotype data of 828 Iranian women who experienced natural menopause. SNP genotyping data were used to perform linear regression analyses with ANM as a quantitative trait. Study participants were drawn from the population-based Tehran Lipid and Glucose Study based in Tehran, Iran. This study was performed between February 2009 and March 2012. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Based on an ANM-GWAS literature review, eight SNPs at four loci previously associated with ANM in European women were tested for replication in Iranian women. Linear regression analyses were performed including (n = 828) and excluding (n = 783) women who experience premature ovarian failure (ANM before 40 years of age). In addition, to search for novel population-specific ANM risk alleles, a pool-based GWAS was performed using this collection of Iranian women. Two DNA pools were constructed and compared: an 'early' ANM pool (lower 20(th) percentile of menopause ages, 40-45 years, n = 165) and a 'late' ANM pool (upper 20(th) percentile of menopause ages, 54-65 years, n = 187). Each DNA pool was assayed on four Illumina Human1M-Duo arrays, and allele-based tests of association were used to rank SNPs. One hundred and two highly ranked SNPs were chosen for individual genotyping by Sequenom MassARRAY and association analysis in the Iranian women. MAIN RESULTS AND THE ROLE OF CHANCE: One SNP-ANM association previously detected in European women was replicated in Iranian women (rs16991615; β = 1.07, standard error (SE): 0.49, P = 0.02). SNPs at the previously reported 19q13.42 and 6p24.2 loci also approached statistical significance and had consistent SNP effects (magnitude and direction) in Iranian women (rs1172822; β = -0.39, SE: 0.22, P = 0.08; and rs2153157, β = 0.41, SE: 0.21, P = 0.05). We found little evidence for novel SNP-ANM associations in Iranian women; no SNP selected based on the pool-based GWAS achieved genome-wide significance. LIMITATIONS, REASONS FOR CAUTION: Due to small sample size this study was powered to reliably detect only moderate-to-large SNP effect sizes. This limited our ability to replicate many of the previously reported SNP-ANM risk alleles and to discover novel SNP-ANM associations' specific to the Iranian population. In performing our pool-based GWAS, a reduction in power was introduced relative to a conventional GWAS. WIDER IMPLICATIONS OF THE FINDINGS: Our results imply that European and Iranian women share ANM-associated genetic variants. Our study was underpowered but for all SNPs tested the direction of the effect was consistent with data from the European study. Therefore, we anticipate that many (if not all) of the ANM-associated SNPs discovered in European women will replicate in Iranian women upon genotyping a sufficient number of women. Our data do not support the hypothesis that population-specific SNP-ANM associations explain population-specific differences in the mean ANM. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Research Institute for Endocrine Sciences. The authors have no conflicts of interest to declare.

PMID: 23592221 [PubMed - as supplied by publisher]

Noncoding variation of the gene for ferritin light chain in hereditary and age-related cataract.

Mol Vis. 2013;19:835-44

Authors: Bennett TM, Maraini G, Jin C, Sun W, Hejtmancik JF, Shiels A

Abstract
PURPOSE: Cataract is a clinically and genetically heterogeneous disorder of the ocular lens and an important cause of visual impairment. The aim of this study was to map and identify the gene underlying autosomal dominant cataract segregating in a four-generation family, determine the lens expression profile of the identified gene, and test for its association with age-related cataract in a case-control cohort.
METHODS: Genomic DNA was prepared from blood leukocytes, and genotyping was performed by means of single-nucleotide polymorphism markers and microsatellite markers. Linkage analyses were performed using the GeneHunter and MLINK programs, and mutation detection was achieved by dideoxy cycle sequencing. Lens expression studies were performed using reverse-transcription polymerase chain reaction (RT-PCR) and in situ hybridization.
RESULTS: Genome-wide linkage analysis with single nucleotide polymorphism markers in the family identified a likely disease-haplotype interval on chromosome 19q (rs888861-[~17Mb]-rs8111640) that encompassed the microsatellite marker D19S879 (logarithm of the odds score [Z]=2.03, recombination distance [θ]=0). Mutation profiling of positional-candidate genes detected a heterozygous, noncoding G-to-T transversion (c.-168G>T) located in the iron response element (IRE) of the gene coding for ferritin light chain (FTL) that cosegregated with cataract in the family. Serum ferritin levels were found to be abnormally elevated (~fourfold), without evidence of iron overload, in an affected family member; this was consistent with a diagnosis of hereditary hyperferritinemia-cataract syndrome. No sequence variations located within the IRE were detected in a cohort of 197 cases with age-related cataract and 102 controls with clear lenses. Expression studies of human FTL, and its mouse counterpart FTL1, in the lens detected RT-PCR amplicons containing full-length protein-coding regions, and strong in situ localization of FTL1 transcripts to the lens equatorial epithelium and peripheral cortex.
CONCLUSIONS: The data are consistent with robust transcription of FTL in the lens, and suggest that whereas variations clustered in the IRE of the FTL gene are directly associated with hereditary hyperferritinemia-cataract syndrome, such IRE variations are unlikely to play a significant role in the genetic etiology of age-related cataract.

PMID: 23592921 [PubMed - in process]

Revising a personal genome by comparing and combining data from two different sequencing platforms.

PLoS One. 2013;8(4):e60585

Authors: Kim D, Kim WY, Lee SY, Lee SY, Yun H, Shin SY, Lee J, Hong Y, Won Y, Kim SJ, Lee YS, Ahn SM

Abstract
For the robust practice of genomic medicine, sequencing results must be compatible, regardless of the sequencing technologies and algorithms used. Presently, genome sequencing is still an imprecise science and is complicated by differences in the chemistry, coverage, alignment, and variant-calling algorithms. We identified ∼3.33 million single nucleotide variants (SNVs) and ∼3.62 million SNVs in the SJK genome using SOLiD and Illumina data, respectively. Approximately 3 million SNVs were concordant between the two platforms while 68,532 SNVs were discordant; 219,616 SNVs were SOLiD-specific and 516,080 SNVs were Illumina-specific (i.e., platform-specific). Concordant, discordant, and platform-specific SNVs were further analyzed and characterized. Overall, a large portion of heterozygous SNVs that were discordant with genotyping calls of single nucleotide polymorphism chips were highly confident. Approximately 70% of the platform-specific SNVs were located in regions containing repetitive sequences. Such platform-specificity may arise from differences between platforms, with regard to read length (36 bp and 72 bp vs. 50 bp), insert size (∼100-300 bp vs. ∼1-2 kb), sequencing chemistry (sequencing-by-synthesis using single nucleotides vs. ligation-based sequencing using oligomers), and sequencing quality. When data from the two platforms were merged for variant calling, the proportion of callable regions of the reference genome increased to 99.66%, which was 1.43% higher than the average callability of the two platforms, representing ∼40 million bases. In this study, we compared the differences in sequencing results between two sequencing platforms. Approximately 90% of the SNVs were concordant between the two platforms, yet ∼10% of the SNVs were either discordant or platform-specific, indicating that each platform had its own strengths and weaknesses. When data from the two platforms were merged, both the overall callability of the reference genome and the overall accuracy of the SNVs improved, demonstrating the likelihood that a re-sequenced genome can be revised using complementary data.

PMID: 23593254 [PubMed - in process]