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Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms.
Rusu V, Hoch E, Mercader JM, Tenen DE, Gymrek M, Hartigan CR, DeRan M, von Grotthuss M, Fontanillas P, Spooner A, Guzman G, Deik AA, Pierce KA, Dennis C, Clish CB, Carr SA, Wagner BK, Schenone M, Ng MCY, Chen BH, MEDIA Consortium, SIGMA T2D Consortium, Centeno-Cruz F, Zerrweck C, Orozco L, Altshuler DM, Schreiber SL, Florez JC, Jacobs SBR, Lander ES
(2017) Cell 170: 199-212.e20
MeSH Terms: Basigin, Cell Membrane, Chromosomes, Human, Pair 17, Diabetes Mellitus, Type 2, Gene Knockdown Techniques, Haplotypes, Hepatocytes, Heterozygote, Histone Code, Humans, Liver, Models, Molecular, Monocarboxylic Acid Transporters
Show Abstract · Added September 20, 2017
Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. VIDEO ABSTRACT.
Copyright © 2017 Elsevier Inc. All rights reserved.
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13 MeSH Terms
Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.
Permuth-Wey J, Lawrenson K, Shen HC, Velkova A, Tyrer JP, Chen Z, Lin HY, Chen YA, Tsai YY, Qu X, Ramus SJ, Karevan R, Lee J, Lee N, Larson MC, Aben KK, Anton-Culver H, Antonenkova N, Antoniou AC, Armasu SM, Australian Cancer Study, Australian Ovarian Cancer Study, Bacot F, Baglietto L, Bandera EV, Barnholtz-Sloan J, Beckmann MW, Birrer MJ, Bloom G, Bogdanova N, Brinton LA, Brooks-Wilson A, Brown R, Butzow R, Cai Q, Campbell I, Chang-Claude J, Chanock S, Chenevix-Trench G, Cheng JQ, Cicek MS, Coetzee GA, Consortium of Investigators of Modifiers of BRCA1/2, Cook LS, Couch FJ, Cramer DW, Cunningham JM, Dansonka-Mieszkowska A, Despierre E, Doherty JA, Dörk T, du Bois A, Dürst M, Easton DF, Eccles D, Edwards R, Ekici AB, Fasching PA, Fenstermacher DA, Flanagan JM, Garcia-Closas M, Gentry-Maharaj A, Giles GG, Glasspool RM, Gonzalez-Bosquet J, Goodman MT, Gore M, Górski B, Gronwald J, Hall P, Halle MK, Harter P, Heitz F, Hillemanns P, Hoatlin M, Høgdall CK, Høgdall E, Hosono S, Jakubowska A, Jensen A, Jim H, Kalli KR, Karlan BY, Kaye SB, Kelemen LE, Kiemeney LA, Kikkawa F, Konecny GE, Krakstad C, Kjaer SK, Kupryjanczyk J, Lambrechts D, Lambrechts S, Lancaster JM, Le ND, Leminen A, Levine DA, Liang D, Lim BK, Lin J, Lissowska J, Lu KH, Lubiński J, Lurie G, Massuger LF, Matsuo K, McGuire V, McLaughlin JR, Menon U, Modugno F, Moysich KB, Nakanishi T, Narod SA, Nedergaard L, Ness RB, Nevanlinna H, Nickels S, Noushmehr H, Odunsi K, Olson SH, Orlow I, Paul J, Pearce CL, Pejovic T, Pelttari LM, Pike MC, Poole EM, Raska P, Renner SP, Risch HA, Rodriguez-Rodriguez L, Rossing MA, Rudolph A, Runnebaum IB, Rzepecka IK, Salvesen HB, Schwaab I, Severi G, Shridhar V, Shu XO, Shvetsov YB, Sieh W, Song H, Southey MC, Spiewankiewicz B, Stram D, Sutphen R, Teo SH, Terry KL, Tessier DC, Thompson PJ, Tworoger SS, van Altena AM, Vergote I, Vierkant RA, Vincent D, Vitonis AF, Wang-Gohrke S, Palmieri Weber R, Wentzensen N, Whittemore AS, Wik E, Wilkens LR, Winterhoff B, Woo YL, Wu AH, Xiang YB, Yang HP, Zheng W, Ziogas A, Zulkifli F, Phelan CM, Iversen E, Schildkraut JM, Berchuck A, Fridley BL, Goode EL, Pharoah PD, Monteiro AN, Sellers TA, Gayther SA
(2013) Nat Commun 4: 1627
MeSH Terms: Carcinoma, Ovarian Epithelial, Chromosomes, Human, Pair 17, Female, Genetic Predisposition to Disease, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide
Show Abstract · Added March 18, 2014
Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.
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8 MeSH Terms
Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.
Lan Q, Hsiung CA, Matsuo K, Hong YC, Seow A, Wang Z, Hosgood HD, Chen K, Wang JC, Chatterjee N, Hu W, Wong MP, Zheng W, Caporaso N, Park JY, Chen CJ, Kim YH, Kim YT, Landi MT, Shen H, Lawrence C, Burdett L, Yeager M, Yuenger J, Jacobs KB, Chang IS, Mitsudomi T, Kim HN, Chang GC, Bassig BA, Tucker M, Wei F, Yin Z, Wu C, An SJ, Qian B, Lee VH, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Kim JH, Gao YT, Tsai YH, Jung YJ, Guo H, Hu Z, Hutchinson A, Wang WC, Klein R, Chung CC, Oh IJ, Chen KY, Berndt SI, He X, Wu W, Chang J, Zhang XC, Huang MS, Zheng H, Wang J, Zhao X, Li Y, Choi JE, Su WC, Park KH, Sung SW, Shu XO, Chen YM, Liu L, Kang CH, Hu L, Chen CH, Pao W, Kim YC, Yang TY, Xu J, Guan P, Tan W, Su J, Wang CL, Li H, Sihoe AD, Zhao Z, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Cai Q, Lin CC, Park IK, Xu P, Dong J, Kim C, He Q, Perng RP, Kohno T, Kweon SS, Chen CY, Vermeulen R, Wu J, Lim WY, Chen KC, Chow WH, Ji BT, Chan JK, Chu M, Li YJ, Yokota J, Li J, Chen H, Xiang YB, Yu CJ, Kunitoh H, Wu G, Jin L, Lo YL, Shiraishi K, Chen YH, Lin HC, Wu T, Wu YL, Yang PC, Zhou B, Shin MH, Fraumeni JF, Lin D, Chanock SJ, Rothman N
(2012) Nat Genet 44: 1330-5
MeSH Terms: Adenocarcinoma, Adenocarcinoma of Lung, Adult, Aged, Asian Continental Ancestry Group, Carcinoma, Squamous Cell, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lung Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, Smoking
Show Abstract · Added September 3, 2013
To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
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20 MeSH Terms
Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21.
Haiman CA, Chen GK, Blot WJ, Strom SS, Berndt SI, Kittles RA, Rybicki BA, Isaacs WB, Ingles SA, Stanford JL, Diver WR, Witte JS, Hsing AW, Nemesure B, Rebbeck TR, Cooney KA, Xu J, Kibel AS, Hu JJ, John EM, Gueye SM, Watya S, Signorello LB, Hayes RB, Wang Z, Yeboah E, Tettey Y, Cai Q, Kolb S, Ostrander EA, Zeigler-Johnson C, Yamamura Y, Neslund-Dudas C, Haslag-Minoff J, Wu W, Thomas V, Allen GO, Murphy A, Chang BL, Zheng SL, Leske MC, Wu SY, Ray AM, Hennis AJ, Thun MJ, Carpten J, Casey G, Carter EN, Duarte ER, Xia LY, Sheng X, Wan P, Pooler LC, Cheng I, Monroe KR, Schumacher F, Le Marchand L, Kolonel LN, Chanock SJ, Van Den Berg D, Stram DO, Henderson BE
(2011) Nat Genet 43: 570-3
MeSH Terms: African Americans, Chromosomes, Human, Pair 17, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Prostatic Neoplasms
Show Abstract · Added March 18, 2014
In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.
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8 MeSH Terms
Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients.
Bhatnagar P, Purvis S, Barron-Casella E, DeBaun MR, Casella JF, Arking DE, Keefer JR
(2011) J Hum Genet 56: 316-23
MeSH Terms: African Continental Ancestry Group, Anemia, Sickle Cell, Bayes Theorem, Carrier Proteins, Chromosomes, Human, Pair 17, Cohort Studies, Erythrocyte Count, Erythrocytes, Fetal Hemoglobin, Genome-Wide Association Study, Genotype, Glucagon-Like Peptide-1 Receptor, Haplotypes, Humans, Male, Nuclear Proteins, Polymorphism, Single Nucleotide, Receptors, Glucagon
Show Abstract · Added November 27, 2013
Fetal hemoglobin (HbF) level has emerged as an important prognostic factor in sickle-cell disease (SCD) and can be measured by the proportion of HbF-containing erythrocytes (F-cells). Recently, BCL11A (zinc-finger protein) was identified as a regulator of HbF, and the strongest association signals were observed either directly for rs766432 or for correlated single-nucleotide polymorphisms (SNPs). To identify additional independently associated genetic variants, we performed a genome-wide association study (GWAS) on the proportion of F-cells in individuals of African ancestry with SCD from the Silent Infarct Transfusion (SIT) Trial cohort. Our study not only confirms the association of rs766432 (P-value <3.32 × 10(-13)), but also identifies an independent novel intronic SNP, rs7606173, associated with F-cells (P-value <1.81 × 10(-15)). The F-cell variances explained independently by these two SNPs are ∼13% (rs7606173) and ∼11% (rs766432), whereas, together they explain ∼16%. Additionally, in men, we identify a novel locus on chromosome 17, glucagon-like peptide-2 receptor (GLP2R), associated with F-cell regulation (rs12103880; P-value <3.41 × 10(-8)). GLP2R encodes a G protein-coupled receptor and involved in proliferative and anti-apoptotic cellular responses. These findings highlight the importance of denser genetic screens and suggest further exploration of the BCL11A and GLP2R loci to gain additional insight into HbF/F-cell regulation.
1 Communities
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18 MeSH Terms
The orexins/hypocretins and schizophrenia.
Deutch AY, Bubser M
(2007) Schizophr Bull 33: 1277-83
MeSH Terms: Benzhydryl Compounds, Brain, Central Nervous System Stimulants, Chromosomes, Human, Pair 17, Humans, Intracellular Signaling Peptides and Proteins, Modafinil, Neuropeptides, Orexins, Schizophrenia
Show Abstract · Added May 27, 2014
Advances in molecular biology have led to new peptides and proteins being discovered on a regular basis, including the isolation of a number of neurotransmitter candidates. Rarely, however, do these immediately capture the attention of the scientific community. The isolation and characterization of the orexin/hypocretin peptides a decade ago resulted in a slew of studies that have helped clarified their diverse functions, including prominent roles in arousal and appetitive behavior. A number of recent studies have detailed the role of the orexins/hypocretins in attention and cognition and uncovered an involvement in schizophrenia and the mechanisms of action of antipsychotic drugs (APDs). This issue of Schizophrenia Bulletin presents several articles that review our current understanding and point to future directions for the study of the orexins/hypocretins in schizophrenia and APD actions.
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10 MeSH Terms
Molecular dissection of 17q12 amplicon in upper gastrointestinal adenocarcinomas.
Maqani N, Belkhiri A, Moskaluk C, Knuutila S, Dar AA, El-Rifai W
(2006) Mol Cancer Res 4: 449-55
MeSH Terms: Adenocarcinoma, Chromosomes, Human, Pair 17, Esophageal Neoplasms, Female, Gene Amplification, Gene Dosage, Humans, In Situ Hybridization, Fluorescence, Male, Neoplasm Staging, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms
Show Abstract · Added March 5, 2014
DNA amplification at 17q is frequently detected in upper gastrointestinal adenocarcinomas (UGC; stomach and esophagus). In this study, we did fluorescence in situ hybridization on a tissue microarray that contained 304 UGCs and 89 normal stomach samples using a approximately 168-kb BAC clone (CTD-2019C10) that maps to 17q12-q21.1. This 168-kb region contains the following genes: PPP1R1B/DARPP-32, STARD3, TCAP, PNMT, PERLD1, ERBB2, C17orf37, and GRB7 as well as the first two exons of ZNFN1A3. DNA amplification (> or =5 signals) was detected in 85 of 282 (30%) of UGCs, and high-level amplification (> or =10 signals) was seen in 28 of 282 (10%) of all tumors. Adenocarcinomas of gastroesophageal junction and lower esophagus had the highest frequency of amplification (45%) compared with stomach tumors (27%; P = 0.04). On the other hand, 38% of tumors with intestinal-type morphology had amplification compared with 26% of diffuse-type tumors (P = 0.02). We further did quantitative real-time reverse transcription-PCR on 74 frozen tissue samples from UGCs for 11 genes located within or adjacent to the boundaries of this approximately 168-kb genomic region. These genes include all 9 genes that are fully or partially located inside the CTD-2019C10 clone as well as 2 additional adjacent genes (NEUROD and TOP2A). Overexpression of PPP1R1B/DARPP-32, TCAP, and TOP2A was seen in approximately half of the tumors, whereas STARD3 and ZNFN1A3 were rarely overexpressed (12%). Interestingly, there was a statistical correlation between expression of all 8 genes that map between PPP1R1B/DARPP-32 and GRB7, whereas expression of NEUROD, ZNFN1A3, and TOP2A that are partially inside or adjacent to the boundaries of the CTD-2019C10 clone did not correlate with the expression of any of these 8 genes. These data show a transcriptionally active oncogenomic region bounded by PPP1R1B/DARPP-32 and GRB7 in UGCs and provide further insight into expression levels of several critical genes.
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13 MeSH Terms
Diminished taxol/GTP-stimulated tubulin polymerization in diseased region of brain from patients with late-onset or inherited Alzheimer's disease or frontotemporal dementia with parkinsonism linked to chromosome-17 but not individuals with mild cognitive impairment.
Boutté AM, Neely MD, Bird TD, Montine KS, Montine TJ
(2005) J Alzheimers Dis 8: 1-6
MeSH Terms: Aged, Aged, 80 and over, Alzheimer Disease, Brain, Chromosomes, Human, Pair 17, Cognition Disorders, DNA Mutational Analysis, Dementia, Female, Genetic Linkage, Humans, Male, Membrane Proteins, Microtubule-Associated Proteins, Microtubules, Paclitaxel, Parkinsonian Disorders, Presenilin-2, Tubulin, Tubulin Modulators, tau Proteins
Show Abstract · Added September 13, 2014
Neuronal microtubules are morphologically abnormal in diseased regions of brain from patients with late-onset Alzheimer's disease (LOAD). Here we tested the hypothesis that tubulin derived from gray matter of patients with multiple forms of dementia was functionally impaired. Following taxol/GTP stimulation of tubulin polymerization of gray matter extracts we observed reduced capacity of tubulin to polymerize in LOAD, but not individuals with mild cognitive impairment (MCI), compared to controls. Moreover, we observed similarly reduced taxol/GTP-stimulated tubulin polymerization from gray matter obtained from patients with AD caused by PSEN2 N141I mutation or frontotemporal dementia with parkinsonism linked to chromosome-17 caused (FTDP-17) by TAU V337M or P301L mutation. Our results show that modification of tubulin function may contribute to intermediate or late stages in the pathogenesis of sporadic and inherited AD as well as FTDP-17.
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21 MeSH Terms
Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors.
Sutcliffe JS, Delahanty RJ, Prasad HC, McCauley JL, Han Q, Jiang L, Li C, Folstein SE, Blakely RD
(2005) Am J Hum Genet 77: 265-79
MeSH Terms: Alanine, Alleles, Autistic Disorder, Blood Platelets, Chromosomes, Human, Pair 17, Compulsive Behavior, Exons, Family Health, Female, Gene Deletion, Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Glycine, Humans, Introns, Linkage Disequilibrium, Male, Membrane Glycoproteins, Membrane Transport Proteins, Models, Genetic, Nerve Tissue Proteins, Pedigree, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Risk, Serotonin, Serotonin Plasma Membrane Transport Proteins, Time Factors
Show Abstract · Added February 20, 2014
Autism is a spectrum of neurodevelopmental disorders with a primarily genetic etiology exhibiting deficits in (1) development of language and (2) social relationships and (3) patterns of repetitive, restricted behaviors or interests and resistance to change. Elevated platelet serotonin (5-HT) in 20%-25% of cases and efficacy of selective 5-HT reuptake inhibitors (SSRIs) in treating anxiety, depression, and repetitive behaviors points to the 5-HT transporter (5-HTT; SERT) as a strong candidate gene. Association studies involving the functional insertion/deletion polymorphism in the promoter (5-HTTLPR) and a polymorphism in intron 2 are inconclusive, possibly because of phenotypic heterogeneity. Nonetheless, mounting evidence for genetic linkage of autism to the chromosome 17q11.2 region that harbors the SERT locus (SLC6A4) supports a genetic effect at or near this gene. We confirm recent reports of sex-biased genetic effects in 17q by showing highly significant linkage driven by families with only affected males. Association with common alleles fails to explain observed linkage; therefore, we hypothesized that preferential transmission of multiple alleles does explain it. From 120 families, most contributing to linkage at 17q11.2, we found four coding substitutions at highly conserved positions and 15 other variants in 5' noncoding and other intronic regions transmitted in families exhibiting increased rigid-compulsive behaviors. In the aggregate, these variants show significant linkage to and association with autism. Our data provide strong support for a collection of multiple, often rare, alleles at SLC6A4 as imposing risk of autism.
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30 MeSH Terms
Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates.
McCauley JL, Li C, Jiang L, Olson LM, Crockett G, Gainer K, Folstein SE, Haines JL, Sutcliffe JS
(2005) BMC Med Genet 6: 1
MeSH Terms: Adolescent, Adult, Autistic Disorder, Child, Child, Preschool, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 19, Female, Genetic Linkage, Genetic Predisposition to Disease, Genome, Human, Humans, Male, Middle Aged, Phenotype
Show Abstract · Added February 20, 2014
BACKGROUND - Autism is a neurobehavioral spectrum of phenotypes characterized by deficits in the development of language and social relationships and patterns of repetitive, rigid and compulsive behaviors. Twin and family studies point to a significant genetic etiology, and several groups have performed genomic linkage screens to identify susceptibility loci.
METHODS - We performed a genome-wide linkage screen in 158 combined Tufts, Vanderbilt and AGRE (Autism Genetics Research Exchange) multiplex autism families using parametric and nonparametric methods with a categorical autism diagnosis to identify loci of main effect. Hypothesizing interdependence of genetic risk factors prompted us to perform exploratory studies applying the Ordered-Subset Analysis (OSA) approach using LOD scores as the trait covariate for ranking families. We employed OSA to test for interlocus correlations between loci with LOD scores > or =1.5, and empirically determined significance of linkage in optimal OSA subsets using permutation testing. Exploring phenotypic correlates as the basis for linkage increases involved comparison of mean scores for quantitative trait-based subsets of autism between optimal subsets and the remaining families.
RESULTS - A genome-wide screen for autism loci identified the best evidence for linkage to 17q11.2 and 19p13, with maximum multipoint heterogeneity LOD scores of 2.9 and 2.6, respectively. Suggestive linkage (LOD scores > or =1.5) at other loci included 3p, 6q, 7q, 12p, and 16p. OSA revealed positive correlations of linkage between the 19p locus and 17q, between 19p and 6q, and between 7q and 5p. While potential phenotypic correlates for these findings were not identified for the chromosome 7/5 combination, differences indicating more rapid achievement of "developmental milestones" was apparent in the chromosome 19 OSA-defined subsets for 17q and 6q. OSA was used to test the hypothesis that 19p linkage involved more rapid achievement of these milestones and it revealed significantly increased LOD* scores at 19p13.
CONCLUSIONS - Our results further support 19p13 as harboring an autism susceptibility locus, confirm other linkage findings at 17q11.2, and demonstrate the need to analyze more discreet trait-based subsets of complex phenotypes to improve ability to detect genetic effects.
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15 MeSH Terms