Search results for "Allele"
showing 10 items of 1006 documents
Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.
2012
Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on …
A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2
2009
BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-ana…
Italian familial defective apolipoprotein B patients share a unique haplotype with other Caucasian patients.
2001
Familial defective apolipoprotein (apo) B-100 together with familial hypercholesterolemia are the two common genetic conditions that cause hypercholesterolemia. Familial defective apolipoprotein B-100 is due to mutations around codon 3500 of the apo B gene. The most-characterized mutation is a G>A transition at nucleotide 10,708 that results in the substitution of arginine by glutamine at codon 3500 (Apo B Arg3500Gln). Two other mutations are caused by a C>T transition, one at nucleotide 10,800 (Apo B Arg3531Cys) and the other at nucleotide 10,707 (apo B Arg3500Trp). In the present study we describe three new Italian cases of familial defective apolipoprotein B-100 (Apo B Arg3500Gln), one f…
HUMAN LEUKOCYTE ANTIGEN POLYMORPHISMS IN ITALIAN PRIMARY BILIARY CIRRHOSIS: A MULTICENTER STUDY OF 664 PATIENTS AND 1992 HEALTHY CONTROLS
2008
Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multicenter case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and sex, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR), 3.3; 95% confidence interval (CI), 2.4-4.5] and DRB1*02 (OR 0.9; 95% CI 0.8-1.2) …
BBS1 Mutations in a Wide Spectrum of Phenotypes Ranging From Nonsyndromic Retinitis Pigmentosa to Bardet-Biedl Syndrome
2012
OBJECTIVE: To investigate the involvement of the Bardet-Biedl syndrome (BBS) gene BBS1 p.M390R variant in nonsyndromic autosomal recessive retinitis pigmentosa (RP). METHODS: Homozygosity mapping of a patient with isolated RP was followed by BBS1 sequence analysis. We performed restriction fragment length polymorphism analysis of the p.M390R allele in 2007 patients with isolated RP or autosomal recessive RP and in 1824 ethnically matched controls. Patients with 2 BBS1 variants underwent extensive clinical and ophthalmologic assessment. RESULTS: In an RP proband who did not fulfill the clinical criteria for BBS, we identified a large homozygous region encompassing the BBS1 gene, which carrie…
Intelligence in DSM-IV combined type attention-deficit/hyperactivity disorder is not predicted by either dopamine receptor/transporter genes or other…
2008
Contains fulltext : 69677.pdf (Publisher’s version ) (Closed access) A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large ra…
Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD
2008
Contains fulltext : 70183.pdf (Publisher’s version ) (Closed access) Previous studies have found heterogeneous association between DAT1-3'-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identi…
Inheritance and variable expression in Rubinstein-Taybi syndrome.
2010
Familial Rubinstein-Taybi syndrome (RTS) is very rare. Here we report on the 6th and 7th case of inherited RTS. Family 1 presents with incomplete or mild RTS over three generations; a 13-year-old girl (proband 1) with mild but typical facial features and learning disabilities, her very mildly affected mother (proband 2), and the maternal grandmother (proband 3). Family 2 includes three females with classical RTS (probands 4-6) and their father (proband 7) with broad thumbs and halluces. Proband 5 also had a brain tumor (ganglioglioma) at the age of 3 years. In probands 1-3, direct sequencing identified a novel CREBBP missense mutation, c.2728A > G (predicting p.Thr910Ala), that was absent i…
Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment.
2006
New technology enables expansion of newborn screening (NBS) of inborn errors aimed to prevent adverse outcome. In conditions with a large share of asymptomatic phenotypes, the potential harm created by NBS must carefully be weighed against benefit. Policies vary throughout the United States, Australia, and Europe due to limited data on outcome and treatability of candidate screening conditions. We elaborated the rationale for decision making in 3-methylcrotonyl-coenzyme A (CoA) carboxylase deficiency (MCCD), which afflicts leucine catabolism, with reported outcomes ranging from asymptomatic to death. In Bavaria, we screened 677,852 neonates for 25 conditions, including MCCD, based on elevat…
PRENATAL IDENTIFICATION OF A HETEROZYGOUS STATUS IN TWO FETUSES AT RISK FOR GLUCOSE–GALACTOSE MALABSORPTION
1996
Glucose-galactose malabsorption (GGM) is an autosomal recessive disorder which presents with severe osmotic diarrhoea shortly after birth. Two proband siblings with GGM were previously demonstrated to contain a missense mutation (D28N) in the Na + -dependent glucose/galactose cotransporter (SGLTI) that accounts for the defect in sugar absorption. Prenatal screening for GGM was performed in two subsequent pregnancies in this large consanguineous family. The first exon of the SGLTI gene was PCR-amplified from genomic DNA and screened for the presence of the D28N mutation by EcoRV restriction digestion. The proband's sibling was heterozygous and a cousin was not a carrier of the D28N mutation.…