Guy A. Rouleau

Bio: Guy A. Rouleau is an academic researcher from Montreal Neurological Institute and Hospital. The author has contributed to research in topics: Genome-wide association study & Amyotrophic lateral sclerosis. The author has an hindex of 129, co-authored 884 publications receiving 65892 citations. Previous affiliations of Guy A. Rouleau include Utrecht University & University of Helsinki.

Short GCG expansions in the PAB II gene for oculopharyngeal muscular dystrophy and diagnostic thereof

Abstract: The present invention relates to a human PAB II gene containing transcribed polymorphic GCG repeat, which comprises a sequence as set forth in SEQ ID NO:3, which includes introns and flanking genomic sequence. The allelic variants of GCG repeat of the human PAB II gene are associated with a disease related with protein accumulation in nucleus, such as polyalanine accumulation, a disease related with swallowing difficulties, such as oculopharyngeal muscular dystrophy. The present invention also relates to a method for the diagnosis of a disease with protein accumulation in nucleus, which comprises the steps of: a) obtaining a nucleic acid sample of said patient; and b) determining allelic variants of GCG repeat of the gene of claim 1, and wherein long allelic variants are indicative of a disease related with protein accumulation in nucleus.

Polymorphic cag repeat-containing gene and uses thereof

Abstract: The present invention relates to hGT1 gene, a polymorphic CAG repeat-containing gene and its uses thereof for the diagnosis, prognosis and treatment of psychiatric diseases, such as schizophrenia.

Successful treatment of psychosis in a patient with Kufor-Rakeb syndrome with low dose aripiprazole: a case report

Abstract: We present a case of a 32-year-old male with Kufor-Rakeb syndrome (KRS), a form of juvenile parkinsonism due to mutations of the ATP13A2 gene at PARK9 locus. The patient was seen for daily ...

Post-concussion symptoms and chronic pain after mild traumatic brain injury are modulated by multiple locus effect in the BDNF gene through the expression of antisense: A pilot prospective control study

Abstract: Background: Mild traumatic brain injury (mTBI) often results in post-concussion symptoms, chronic pain, and sleepiness. Genetic factors are thought to play an important role in poor prognosis.Aims: The aims of this study are to (1) document the prevalence of pain and post-concussion symptoms in mTBI patients in acute and chronic phases (2) determine whether candidate genes predispose to post-concussive symptoms and pain.Methods: Posttraumatic symptoms, evaluated using the Rivermead Post-Concussion Symptoms Questionnaire, and pain were assessed in 94 mTBI patients in the acute phase as well as in 22 healthy controls. Assessment was repeated in 36 patients after one year who agreed to participate in the follow-up visit. Gene polymorphisms and expression were assessed in mTBI patients and healthy controls.Results: In the acute phase, mTBI patients with pain (69%) presented more psychological symptoms and sleepiness and were less able to return to work than those without pain. At one year, 19% of mTBI...

Association study of DNAJC13, UCHL1, HTRA2, GIGYF2 and EIF4G1 with Parkinson’s disease

Abstract: Rare mutations in genes originally discovered in multi-generational families have been associated with increased risk of Parkinson9s Disease (PD). The involvement of rare variants in DNAJC13, UCHL1, HTRA2, GIGYF2 and EIF4G1 loci have been poorly studied or produced conflicting results across cohorts. However, they are still being often referred to as "PD-genes" and used in different models. To further elucidate the role of these five genes in PD, we fully sequenced them using molecular inversion probes in 2,408 PD patients and 3,444 controls from 3 different cohorts. A total of 788 rare variants were identified across the five genes and three cohorts. Burden analyses and optimized sequence Kernel association tests revealed no significant association between any of the genes and PD after correction for multiple comparisons. Our results do not support an association of the five tested genes with PD. Combined with previous studies, it is unlikely that any of these genes plays an important role in PD. Their designation as "PARK" genes should be reconsidered.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

A framework for variation discovery and genotyping using next-generation DNA sequencing data

Abstract: Recent advances in sequencing technology make it possible to comprehensively catalogue genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (1) initial read mapping; (2) local realignment around indels; (3) base quality score recalibration; (4) SNP discovery and genotyping to find all potential variants; and (5) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We discuss the application of these tools, instantiated in the Genome Analysis Toolkit (GATK), to deep whole-genome, whole-exome capture, and multi-sample low-pass (~4×) 1000 Genomes Project datasets.

Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis

Abstract: Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families.

Genetic alterations during colorectal-tumor development.

Abstract: Because most colorectal carcinomas appear to arise from adenomas, studies of different stages of colorectal neoplasia may shed light on the genetic alterations involved in tumor progression. We looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 colorectal-tumor specimens representing various stages of neoplastic development. The specimens consisted of 40 predominantly early-stage adenomas from 7 patients with familial adenomatous polyposis, 40 adenomas (19 without associated foci of carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 92 carcinomas resected from 89 patients. We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial adenomatous polyposis were not lost in adenomas from the patients with polyposis but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from other patients. A specific region of chromosome 18 was deleted frequently in carcinomas (73 percent) and in advanced adenomas (47 percent) but only occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p sequences were usually lost only in carcinomas (75 percent). The four molecular alterations accumulated in a fashion that paralleled the clinical progression of tumors. These results are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumorigenesis.