Evolution of Genomic Structures on Mammalian Sex Chromosomes

Throughout mammalian evolution, recombination between the two sex chromosomes was suppressed in a stepwise manner. It is thought that the suppression of recombination led to an accumulation of deleterious mutations and frequent genomic rearrangements on the Y chromosome. In this article, we review three evolutionary aspects related to genomic rearrangements and structures, such as inverted repeats (IRs) and palindromes (PDs), on the mammalian sex chromosomes. First, we describe the stepwise manner in which recombination between the X and Y chromosomes was suppressed in placental mammals and discuss a genomic rearrangement that might have led to the formation of present pseudoautosomal boundaries (PAB). Second, we describe ectopic gene conversion between the X and Y chromosomes, and propose possible molecular causes. Third, we focus on the evolutionary mode and timing of PD formation on the X and Y chromosomes. The sequence of the chimpanzee Y chromosome was recently published by two groups. Both groups suggest that rapid evolution of genomic structure occurred on the Y chromosome. Our re-analysis of the sequences confirmed the species-specific mode of human and chimpanzee Y chromosomal evolution. Finally, we present a general outlook regarding the rapid evolution of mammalian sex chromosomes

Group involvement and self-rated health among the Japanese elderly: an examination of bonding and bridging social capital

Background: To date, only a small amount of research on bonding/bridging social capital has separately examined their effects on health though they have been thought to have differential effects on health outcomes. By using a large population-based sample of elderly Japanese people, we sought to investigate the association between bonding and bridging social capital and self-rated health for men and women separately. Methods: In August 2010, questionnaires were sent to all residents aged >= 65 years in three municipalities in Okayama prefecture (n = 21232), and 13929 questionnaires were returned (response rate: 65.6%). Social capital was measured from survey responses to questions on participation in six different types of groups: a) the elderly club or sports/hobby/culture circle; b) alumni association; c) political campaign club; d) citizen's group or environmental preservation activity; e) community association; and f) religious organization. Participant perception of group homogeneity (gender, age, and previous occupation) was used to divide social capital into bonding or bridging. Odds ratios (ORs) and 95% confidence intervals (CIs) for poor self-rated health were calculated. Results: A total of 11146 subjects (4441 men and 6705 women) were available for the analysis. Among men, bonding and bridging social capital were inversely associated with poor self-rated health (high bonding social capital; OR: 0.55, 95% CI: 0.31-0.99; high bridging social capital; OR: 0.62, 95% CI: 0.48-0.81) after adjusting for age, educational attainment, smoking status, frequency of alcohol consumption, overweight, living arrangements, and type-D personality. The beneficial effect among women was more likely limited to bonding social capital (high bonding social capital; OR: 0.34, 95% CI: 0.12-1.00), and the association between bridging social capital and self-rated health was less clear (high bridging social capital; OR: 0.69, 95% CI: 0.44-1.07). Conclusions: Bonding/bridging social capital could have differential associations with self-rated health among the Japanese elderly depending on the individual's sex. Considering the lack of consensus on how to measure bonding and bridging social capital, however, we need to carefully assess the generalizability of our findings. Further research is warranted to identify health-relevant dimensions of social capital in different cultural or economic settings

Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

<p>Abstract</p> <p>Background</p> <p>Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (<it>p-</it>distance) between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the <it>p</it>-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes <it>KALX </it>and <it>VCX</it>, in the middle of stratum 4 shows a significantly lower <it>p</it>-distance (1-5%), suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low <it>p</it>-distance region, sequences of a corresponding region including <it>KALX</it>/<it>Y </it>from seven species of non-human primates were analyzed.</p> <p>Results</p> <p>Phylogenetic analysis of this low <it>p</it>-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (<it>i.e</it>., Old World monkeys and hominoids). A <it>KALY</it>-converted <it>KALX </it>allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low <it>p</it>-distance region is located in a <it>LINE </it>element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near <it>VCX</it>, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes.</p> <p>Conclusion</p> <p>Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the evolutionary course of primates. An insertion of a <it>LINE </it>element at the proximal end of the region may be a cause for these frequent conversions. This gene conversion in humans may also be one of the genetic causes of Kallmann syndrome.</p

Association between FSH, E1, and E2 levels in urine and serum in premenopausal and postmenopausal women

Objective: We aimed to establish correlations for the levels of follicle-stimulating hormone (FSH), estrone (E1) and estradiol (E2) between urine and serum in premenopausal and postmenopausal women using immunoassays. Methods: In this study of 92 women (61 postmenopausal, 31 premenopausal), both urine and blood specimens were collected on the same day and stored at 4 °C for analysis by chemiluminescent immunoassay, radioimmunoassay and/or electrochemiluminescent immunoassay. Results: There were correlations in the levels of FSH, E1 and E2 between urine and serum in both postmenopausal (r = 0.96 for FSH, r = 0.91 for E1, r = 0.80 for E2) and premenopausal (r = 0.98 for FSH, r = 0.92 for E1, r = 0.90 for E2) women. It is indicated that the correlations were stronger in the premenopausal group compared with the postmenopausal group, especially for FSH. Conclusion: The levels of FSH, E1 and E2 in urine correlated with those in the serum in premenopausal and postmenopausal women. Urine samples could be used instead of serum samples to measure hormone levels, which would reduce the difficulty of conducting large survey studies

Quantitative determination, by real-time reverse transcription polymerase chain reaction, of aromatase mRNA in invasive ductal carcinoma of the breast

BACKGROUND: Estrogen is a mitogenic factor that is implicated in the genesis and progression of breast cancer via its binding to estrogen receptor (ER)-α. Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase. Previous studies comparing the relative contributions from tumor cells and stromal cells to local estrogen synthesis, as assessed by immunohistochemical analysis, were quite controversial and no consistent relationship was found between the presence of aromatase and any clinicopathologic factor. In addition, previous studies into aromatase gene expression and clinicopathologic factors are limited. METHODS: We assessed the level of expression of aromatase mRNA, using quantitative real-time RT-PCR, in 162 cases of invasive ductal carcinoma of the breast. Associations between aromatase expression and different clinicopathologic factors were sought. RESULTS: It was found that aromatase mRNA was expressed at significantly higher levels in patients older than 50 years, in those without axillary lymph node involvement, in those with tumor size less than 2 cm, and in ER-α positive tumors. However, no relationship was found between aromatase mRNA expression and any other clinicopathologic factor, including histologic grade and progesterone receptor status. Patients with high levels of expression of aromatase mRNA tended to have a better prognosis than did those patients with low expression. CONCLUSION: These findings imply that ER-α and aromatase may be coexpressed in endocrine responsive patients. They may also indicate that aromatase expression could be a marker of endocrine responsiveness, and it may have prognostic implications for breast cancer progression

Genomic structure and evolution of multigene families: “Flowers” on the human genome

We report the results of an extensive investigation of genomic structures in the human genome, with a particular focus on relatively large repeats (>50 kb) in adjacent chromosomal regions. We named such structures “Flowers” because the pattern observed on dot plots resembles a flower. We detected a total of 291 Flowers in the human genome. They were predominantly located in euchromatic regions. Flowers are gene-rich compared to the average gene density of the genome. Genes involved in systems receiving environmental information, such as immunity and detoxification, were overrepresented in Flowers. Within a Flower, the mean number of duplication units was approximately four. The maximum and minimum identities between homologs in a Flower showed different distributions; the maximum identity was often concentrated to 100% identity, while the minimum identity was evenly distributed in the range of 78% to 100%. Using a gene conversion detection test, we found frequent and/or recent gene conversion events within the tested Flowers. Interestingly, many of those converted regions contained protein-coding genes. Computer simulation studies suggest that one role of such frequent gene conversions is the elongation of the life span of gene families in a Flower by the resurrection of pseudogenes

Comparison of dynamic occlusal contacts during chewing between working and balancing sides

Objectives: Mastication is a crucial function for the elderly, and promotes oral health status, cognitive function and the physical constitution. Most reports about occlusion patterns and occlusal glide of adults have reported the jaw movement at the lower incisal point due to easiness of evaluating masticatory performance. The purpose of this study was to test the hypothesis that dynamic occlusal contact area (OCA) during chewing differ for each tooth on the working vs. the balancing chewing side. Design: In thirteen healthy Japanese females, OCA was estimated with a measurement system combining 3-D tracking of mandibular movements with 3-D digitization of tooth shape. Results: The starting of occlusal contact between teeth at working side and balancing side did not differ significantly. In contrast, ending of occlusal contact of teeth at balancing side were markedly longer than that of teeth at working side at lateral incisor, canine, and first premolar. The dynamic sum of OCAs for all teeth was symmetrical around maximum closed position (MCP) when chewing on the working side. In contrast, the dynamic sum of OCA peaked after MCP when chewing on the balancing side. In working and balancing side, sums of maximum OCA at all posterior teeth accounted for 93%, 86% of sum OCA for all teeth at working and balancing sides, respectively. Conclusion: Our result suggested that the hypothesis that dynamic OCA during chewing differ for each tooth on the working vs. the balancing chewing side was not accepted at molars

Polymorphisms and Body Mass Index Across Life Course

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05/282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways

Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese

BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8 × 10(-10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)--POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)--and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma