Male-specific region of the y chromosome and cardiovascular risk phylogenetic analysis and gene expression studies
- Authors: Bloomer, Lisa , Nelson, Christopher , Eales, James , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Moore, Jasbir , Consortium, Cardiogenics , Zukowska-Szczechowska, Ewa , Goodall, Alison , Thompson, John , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2013
- Type: Text , Journal article
- Relation: Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 33, no. 7 (2013), p. 1722-1727
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
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- Description: Objective-Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the malespecific region may explain this association. Approach and Results-A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had 0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene (UTY) and protein kinase, Y-linked, pseudogene (PRKY) in macrophages (P=0.0001 and P=0.002, respectively). Conclusions-Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors. © 2013 American Heart Association, Inc.
- Description: 2003011132
Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD Searching for an effect of allelic heterogeneity
- Authors: Tovo-Rodrigues, Luciana , Rohde, Luis , Roman, Tatiana , Schmitz, Marcelo , Polanczyk, Guilherme , Zeni, Cristian , Marques, Francine , Contini, Veronica , Grevet, Eugenio , Belmonte-De-Abreu, Paulo , Bau, Claiton , Hutz, Mara
- Date: 2012
- Type: Text , Journal article
- Relation: Molecular Psychiatry Vol. 17, no. 5 (May 2012), p. 520-526
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- Description: Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/ hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P = 0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P = 0.008 for total substitutions and P = 0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.
- Description: C1