Advances in genomics and genetics最新文献

{"title":"Frequency of frontotemporal dementia gene variants in <i>C9ORF72</i>, <i>MAPT</i>, and <i>GRN</i> in academic versus commercial laboratory cohorts.","authors":"Natasha Zr Steele,&nbsp;Alison R Bright,&nbsp;Suzee E Lee,&nbsp;Jamie C Fong,&nbsp;Luke W Bonham,&nbsp;Anna Karydas,&nbsp;Izabela D Karbassi,&nbsp;Mochtar Pribadi,&nbsp;Marc A Meservey,&nbsp;Matthew C Gallen,&nbsp;Eliana Marisa Ramos,&nbsp;Khalida Liaquat,&nbsp;Carol C Hoffman,&nbsp;Meagan R Krasner,&nbsp;Whitney Dodge,&nbsp;Bruce L Miller,&nbsp;Giovanni Coppola,&nbsp;Katherine P Rankin,&nbsp;Jennifer S Yokoyama,&nbsp;Joseph J Higgins","doi":"10.2147/AGG.S164047","DOIUrl":"https://doi.org/10.2147/AGG.S164047","url":null,"abstract":"<p><strong>Background: </strong>Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia, and elucidating its genetic underpinnings is critical. FTLD research centers typically recruit patient cohorts that are limited by the center's specialty and the ways in which its geographic location affects the ethnic makeup of research participants. Novel sources of data are needed to get population estimates of the contribution of variants in known FTLD-associated genes.</p><p><strong>Methods: </strong>We compared FLTD-associated genetic variants in microtubule-associated protein tau (<i>MAPT</i>), progranulin (<i>GRN</i>), and chromosome nine open reading frame 72 (<i>C9ORF72</i>) from an academic research cohort and a commercial clinical genetics laboratory. Pathogenicity was assessed using guidelines of the American College of Medical Genetics and Genomics and a rule-based DNA variant assessment system. We conducted chart reviews on patients with novel or rare disease-associated variants.</p><p><strong>Results: </strong>A total of 387 cases with FTLD-associated variants from the commercial (n=2,082) and 78 cases from the academic cohort (n=2,089) were included for analysis. In the academic cohort, the most frequent pathogenic variants were <i>C9ORF72</i> expansions (63%, n=49), followed by <i>GRN</i> (26%, n=20) and <i>MAPT</i> (11%, n=9). Each gene's contribution to disease was similarly ranked in the commercial laboratory but differed in magnitude: <i>C9ORF72</i> (89%, n=345), <i>GRN</i> (6%, n=24), and <i>MAPT</i> (5%, n=19). Of the 37 unique <i>GRN</i>/<i>MAPT</i> variants identified, only six were found in both cohorts. Clinicopathological data from patients in the academic cohort strengthened classification of two novel <i>GRN</i> variant as pathogenic (p.Pro166Leufs*2, p.Gln406*) and one <i>GRN</i> variant of unknown significance as a possible rare risk variant (p.Cys139Arg).</p><p><strong>Conclusion: </strong>Differences in gene frequencies and identification of unique pathogenic alleles in each cohort demonstrate the importance of data sharing between academia and community laboratories. Using shared data sources with well-characterized clinical phenotypes for individual variants can enhance interpretation of variant pathogenicity and inform clinical management of at-risk patients and families.</p>","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"8 ","pages":"23-33"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AGG.S164047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37368648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-losing enteropathy and joint contractures caused by a novel homozygous ANTXR2 mutation.","authors":"Edith Schussler,&nbsp;Rita V Linkner,&nbsp;Jacob Levitt,&nbsp;Lakshmi Mehta,&nbsp;John A Martignetti,&nbsp;Kimihiko Oishi","doi":"10.2147/AGG.S159077","DOIUrl":"https://doi.org/10.2147/AGG.S159077","url":null,"abstract":"<p><p>Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disorder and an allelic form of hyaline fibromatosis syndrome that is caused by mutations in the <i>ANTRX2</i> gene encoding the transmembrane anthrax toxin receptor 2. Its main features include characteristic skin lesions, joint contractures, persistent diarrhea, and failure to thrive due to accumulation of hyaline material in multiple organs. The resulting severe malnutrition can cause death in early infancy. Because of its rarity and high fatality rate, timely diagnosis is difficult and ISH may be underdiagnosed. In this report, we describe a 10-month-old male with severe protein-losing enteropathy, skin lesions, and painful joint contractures, diagnosed with ISH based on skin his-topathology and identification of a novel homozygous <i>ANTRX2</i> mutation, c.1127_1128delTG (p.V376Gfs*14). While its clinical outcome is poor without curative treatment, establishing a diagnosis of ISH starting from clinical suspicion to molecular analysis is important for appropriate medical management and for risk and carrier assessment of family members.</p>","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"8 ","pages":"17-21"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AGG.S159077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36346887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences between the genomes of lymphoblastoid cell lines and blood-derived samples.","authors":"Lena M Joesch-Cohen, Gustavo Glusman","doi":"10.2147/AGG.S128824","DOIUrl":"10.2147/AGG.S128824","url":null,"abstract":"<p><p>Lymphoblastoid cell lines (LCLs) represent a convenient research tool for expanding the amount of biologic material available from an individual. LCLs are commonly used as reference materials, most notably from the Genome in a Bottle Consortium. However, the question remains how faithfully LCL-derived genome assemblies represent the germline genome of the donor individual as compared to the genome assemblies derived from peripheral blood mononuclear cells. We present an in-depth comparison of a large collection of LCL- and peripheral blood mononuclear cell-derived genomes in terms of distributions of coverage and copy number alterations. We found significant differences in the depth of coverage and copy number calls, which may be driven by differential replication timing. Importantly, these copy number changes preferentially affect regions closer to genes and with higher GC content. This suggests that genomic studies based on LCLs may display locus-specific biases, and that conclusions based on analysis of depth of coverage and copy number variation may require further scrutiny.</p>","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"7 ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AGG.S128824","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35193007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"การพัฒนาเครื่องหมาย ILP จากยีนที่มีความเกี่ยวข้องกับการสังเคราะห์น้ำตาลซูโครสในอ้อย และการศึกษาโครงสร้างพันธุกรรมอ้อย (Development of ILP markers from genes related to sucrose metabolism in sugarcane and genetic structure of sugarcane)","authors":"ณัฐภัทร พงศ์ศิริพัฒน์ Nattapat Pongsiripat, กิตติพัฒน์ อุโฆษกิจ Kittipat Ukoskit","doi":"10.14456/10.14456/TJG.2014.12","DOIUrl":"https://doi.org/10.14456/10.14456/TJG.2014.12","url":null,"abstract":"Intron length polymorphism (ILP) markers were developed from genes involving in sucrose metabolism using data from KEGG pathway and a previous study of microarray. Of 121,301 sugarcane ESTs (42,377 sugarcane assembled sequences and 78,924 singleton ESTs), 91 ESTs with predicted function in sucrose metabolism were obtained. Intron positions were determined by aligning the ESTs with genomic sequences of sorghum. The conserved sequences flanking the intron regions were used to design 195 ILP markers. The ILP markers were deployed to assess population structure of 200 sugarcane cultivars ( Saccharum spp. L.). The polymorphic 89 alleles were detected. The average polymorphism information content (PIC) was 0.23. The number of subpopulations (K) of 200 sugarcane cultivars was two (K=2). Subpopulation I consisted of most sugarcane varieties sharing the common parent of POJ2878 while most sugarcane varieties in subpopulation II related to the common parent of Trojan and Nco310. The ILP markers developed in this study had a potential for utilizing in association mapping of sucrose content in sugarcane. The knowledge of population structure obtained in this study should be useful to future breeding programs for increasing genetic diversity of sugarcane varieties. เครองหมาย intron length polymorphism (ILP) ไดรบการพฒนาจากยนทเกยวของกบการสงเคราะหนำตาลซโครส โดยใชขอมลจาก KEGG pathway และผลการศกษาการทำงานของยนดวยไมโครแอเรย จากขอมลลำดบ      เบส ESTs ของออย 121,301 ลำดบ (42,377 sugarcane assembled sequences และ 78,924 singleton ESTs) สามารถคดเลอก ESTs ทเกยวของกบการสงเคราะหนำตาลซโครสไดทงหมด 91 ลำดบ ทำนายตำแหนงอนทรอนดวยเปรยบเทยบลำดบเบส EST ของออยกบลำดบเบสจโนมของขาวฟาง และออกแบบไพรเมอรทงหมด 195 คไพรเมอรจากบรเวณอนรกษทครอมตำแหนงอนทรอนอย ในการวเคราะหโครงสรางประชากรออย ( Saccharum spp. L.) 200 ตวอยาง พบวาเครองหมาย ILP ตรวจพบแอลลลได 89 แอลลล มคา polymorphism information content (PIC) เฉลย 0.23 ผลการวเคราะหหาจำนวนประชากรยอย ( K ) พบวากลมตวอยางออยแบงออกเปน 2 ประชากรยอย ( K =2) โดยกลมประชากรยอยทหนงมความสมพนธทางเครอญาตกบออยสายพนธ POJ2878 กลมประชากรยอยทสองมความสมพนธทางเครอญาตกบออยสายพนธ Trojan และ NCo310 เครองหมาย ILP ทพฒนาขนในการทดลองนสามารถนำไปใชวเคราะหหาความสมพนธกบระดบนำตาลซโครสในออยได และขอมลโครงสรางพนธกรรมออยทไดจากการทดลองนจะเปนประโยชนสำหรบแนวทางในการขยายฐานพนธกรรมออย","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"3 1","pages":"111-122"},"PeriodicalIF":0.0,"publicationDate":"2015-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89787636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered placental DNA methylation patterns associated with maternal smoking: current perspectives.","authors":"Jennifer Zj Maccani, Matthew A Maccani","doi":"10.2147/AGG.S61518","DOIUrl":"10.2147/AGG.S61518","url":null,"abstract":"<p><p>The developmental origins of health and disease hypothesis states that adverse early life exposures can have lasting, detrimental effects on lifelong health. Exposure to maternal cigarette smoking during pregnancy is associated with morbidity and mortality in offspring, including increased risks for miscarriage, stillbirth, low birth weight, preterm birth, asthma, obesity, altered neurobehavior, and other conditions. Maternal cigarette smoking during pregnancy interferes with placental growth and functioning, and it has been proposed that this may occur through the disruption of normal and necessary placental epigenetic patterns. Epigenome-wide association studies have identified a number of differentially methylated placental genes that are associated with maternal smoking during pregnancy, including <i>RUNX3</i>, <i>PURA</i>, <i>GTF2H2</i>, <i>GCA</i>, <i>GPR135</i>, and <i>HKR1</i>. The placental methylation status of <i>RUNX3</i> and <i>NR3C1</i> has also been linked to adverse infant outcomes, including preterm birth and low birth weight, respectively. Candidate gene analyses have also found maternal smoking-associated placental methylation differences in the <i>NR3C1</i>, <i>CYP1A1</i>, <i>HTR2A</i>, and <i>HSD11B2</i> genes, as well as in the repetitive elements LINE-1 and AluYb8. The differential methylation patterns of several genes have been confirmed to also exhibit altered gene expression patterns, including <i>CYP1A1</i>, <i>CYP19A1</i>, <i>NR3C1</i>, and <i>HTR2A</i>. Placental methylation patterns associated with maternal smoking during pregnancy may be largely gene-specific and tissue-specific and, to a lesser degree, involve global changes. It is important for future research to investigate the mechanistic roles that these differentially methylated genes may play in mediating the association between maternal smoking during pregnancy and disease in later life, as well as to elucidate the potential influence of emerging tobacco product use during pregnancy, including the use of electronic cigarettes, on placental epigenetics.</p>","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"2015 5","pages":"205-214"},"PeriodicalIF":0.0,"publicationDate":"2015-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/58/nihms700129.PMC4507353.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33862764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics and Epigenetics of Eating Disorders.","authors":"C. Bulik, Z. Yilmaz, Andrew J Hardaway","doi":"10.2147/AGG.S55776","DOIUrl":"https://doi.org/10.2147/AGG.S55776","url":null,"abstract":"Eating disorders (EDs) are serious psychiatric conditions influenced by biological, psychological, and sociocultural factors. A better understanding of the genetics of these complex traits and the development of more sophisticated molecular biology tools have advanced our understanding of the etiology of EDs. The aim of this review is to critically evaluate the literature on the genetic research conducted on three major EDs: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). We will first review the diagnostic criteria, clinical features, prevalence, and prognosis of AN, BN, and BED, followed by a review of family, twin, and adoption studies. We then review the history of genetic studies of EDs covering linkage analysis, candidate gene association studies, genome-wide association studies, and the study of rare variants in EDs. Our review also incorporates a translational perspective by covering animal models of ED-related phenotypes. Finally, we review the nascent field of epigenetics of EDs and a look forward to future directions for ED genetic research.","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"13 1","pages":"131-150"},"PeriodicalIF":0.0,"publicationDate":"2015-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AGG.S55776","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68296859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coding and noncoding expression patterns associated with rare obesity-related disorders: Prader-Willi and Alström syndromes.","authors":"Merlin G Butler,&nbsp;Kun Wang,&nbsp;Jan D Marshall,&nbsp;Jürgen K Naggert,&nbsp;Jasmine A Rethmeyer,&nbsp;Sumedha S Gunewardena,&nbsp;Ann M Manzardo","doi":"10.2147/AGG.S74598","DOIUrl":"https://doi.org/10.2147/AGG.S74598","url":null,"abstract":"<p><p>Obesity is accompanied by hyperphagia in several classical genetic obesity-related syndromes that are rare, including Prader-Willi syndrome (PWS) and Alström syndrome (ALMS). We compared coding and noncoding gene expression in adult males with PWS, ALMS, and nonsyndromic obesity relative to nonobese males using readily available lymphoblastoid cells to identify disease-specific molecular patterns and disturbed mechanisms in obesity. We found 231 genes upregulated in ALMS compared with nonobese males, but no genes were found to be upregulated in obese or PWS males and 124 genes were downregulated in ALMS. The metallothionein gene (<i>MT1X</i>) was significantly downregulated in ALMS, in common with obese males. Only the complex <i>SNRPN</i> locus was disturbed (downregulated) in PWS along with several downregulated small nucleolar RNAs (snoRNAs) in the 15q11-q13 region (<i>SNORD116, SNORD109B, SNORD109A, SNORD107</i>). Eleven upregulated and ten downregulated snoRNAs targeting multiple genes impacting rRNA processing, developmental pathways, and associated diseases were found in ALMS. Fifty-two miRNAs associated with multiple, overlapping gene expression disturbances were upregulated in ALMS, and four were shared with obese males but not PWS males. For example, seven passenger strand microRNAs (miRNAs) (miR-93*, miR-373*, miR-29b-2*, miR-30c-1*, miR27a*, miR27b*, and miR-149*) were disturbed in association with six separate downregulated target genes (<i>CD68, FAM102A, MXI1, MYO1D, TP53INP1</i>, and <i>ZRANB1</i>). Cell cycle (eg, <i>PPP3CA</i>), transcription (eg, <i>POLE2</i>), and development may be impacted by upregulated genes in ALMS, while downregulated genes were found to be involved with metabolic processes (eg, <i>FABP3</i>), immune responses (eg, <i>IL32</i>), and cell signaling (eg, <i>IL1B)</i>. The high number of gene and noncoding RNA disturbances in ALMS contrast with observations in PWS and males with nonsyndromic obesity and may reflect the progressing multiorgan pathology of the ALMS disease process.</p>","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"2015 5","pages":"53-75"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AGG.S74598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33075761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From caveman companion to medical innovator: genomic insights into the origin and evolution of domestic dogs.","authors":"Heidi G Parker,&nbsp;Samuel F Gilbert","doi":"10.2147/AGG.S57678","DOIUrl":"https://doi.org/10.2147/AGG.S57678","url":null,"abstract":"<p><p>The phenotypic and behavioral diversity of the domestic dog has yet to be matched by any other mammalian species. In their current form, which comprises more than 350 populations known as breeds, there is a size range of two orders of magnitude and morphological features reminiscent of not only different species but also different phylogenetic families. The range of both appearance and behavior found in the dog is the product of millennia of human interference, and though humans created the diversity it remains a point of fascination to both lay and scientific communities. In this review we summarize the current understanding of the history of dog domestication based on molecular data. We will examine the ways that canine genetic and genomic studies have evolved and look at examples of dog genetics in the light of human disease.</p>","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"5 ","pages":"239-255"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/AGG.S57678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34983621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Genetics of Kidney Stone Disease","authors":"N. Rungroj, Sittideth Sangnual, Oranud Praditsap, C. Nettuwakul, N. Sawasdee, P. Yenchitsomanus","doi":"10.14456/TJG.2014.9","DOIUrl":"https://doi.org/10.14456/TJG.2014.9","url":null,"abstract":"Kidney stone disease (KSD) is a multifactorial disease caused by a complex interaction of genetic and environmental factors. It causes significant morbidity and medical care expenses worldwide, which can be found commonly in tropical territory including Thailand. A majority of kidney stones are composed of calcium and it is usually associated with a metabolic abnormality such as hypercalciurea, hyperoxaurea, hyperphosphaturia, hyperuricosuria, hypocitraturea, and a defect of urinary acidification. However, few defects associated with monogenic forms of KSD have been identified. To date, molecular genetic studies to investigate genetic contribution of multifactorial KSD have been extensively performed and a number of causative genes have been recognized, but they vary among populations. In Thailand, the highest prevalence of KSD was observed in the Northeastern (NE) area. Its etiology and pathogenesis are still obscure and unique characteristics with no conditions of increased urinary solutes such as hypercalciurea, hyperoxaurea, and hyperuricosuria that are different from what has been reported in other ethnic groups are shown. The study to identify causative genes will provide more understanding of pathogenesis underlying KSD and also the unique pathogenesis of KSD in NE Thai patients. These will lead to improved quality and efficiency of patient care, diagnosis, prevention and control of diseases and complications. The knowledge of reported monogenic and multifactorial KSD, and the update on molecular genetic studies to investigate genes responsible for the disease in NE Thai patients are reviewed in this article.","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"23 1","pages":"28-40"},"PeriodicalIF":0.0,"publicationDate":"2014-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81579524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preliminary case study of androgen receptor gene polymorphism association with impulsivity in women with alcoholism.","authors":"Daniel J Mettman, Merlin G Butler, Albert B Poje, Elizabeth C Penick, Ann M Manzardo","doi":"10.2147/AGG.S57771","DOIUrl":"10.2147/AGG.S57771","url":null,"abstract":"<p><strong>Objective: </strong>The <i>androgen receptor</i> (<i>AR</i>) gene, located on the X chromosome, contains a common polymorphism involving cytosine-adenine-guanine (CAG) repeats, which impacts disease and could contribute to the unequal sex ratio in alcoholism. CAG repeats in the <i>AR</i> gene are known to correlate with impulsivity in males. We report the first preliminary study examining the association between the number of CAG repeats and measures of impulsivity in females with chronic alcoholism.</p><p><strong>Methods: </strong>A total of 35 women and 85 men with chronic alcoholism were previously recruited for a nutritional clinical trial, and 26 well-characterized females (19 African-American and seven Caucasian) with alcoholism agreed to participate for genetic testing. Genomic deoxyribonucleic acid (DNA) was isolated from peripheral blood and CAG repeats determined by analyzing polymerase chain reaction (PCR)-amplified products, using the polymorphic <i>AR</i> gene assay. CAG repeat length was correlated with raw scores from the Barratt Impulsivity Scale, version 11 and the Alcoholism Severity Scale.</p><p><strong>Results: </strong>CAG repeat lengths were significantly longer in Caucasian alcoholic women compared with African-Americans, and the average number of CAG repeats were significantly, positively correlated (<i>P</i><0.05) with impulsivity scores. Women with average CAG repeat length (CAG_ave) ≥18, representing the upper quartile of the repeat range, showed significantly greater mean raw impulsivity scores. CAG repeat length appeared to have less effect in African-American compared with Caucasian women, possibly due to a shorter average repeat length.</p><p><strong>Conclusion: </strong>We found an association between the number of CAG repeats and impulsivity in females with chronic alcoholism, specifically in women with CAG_ave ≥18, seen more commonly in Caucasian compared with African-American women.</p>","PeriodicalId":89652,"journal":{"name":"Advances in genomics and genetics","volume":"4 ","pages":"5-13"},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/aa/nihms573359.PMC4067054.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32456212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}