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Update on the genetics and genomics of PBC.

ABSTRACT: Despite recent progress, the pathogenic mechanisms governing PBC development, treatment response and outcome remain unknown. This deficiency is in large part due to the complex nature of PBC, wherein various environmental factors may be capable of prompting disease, but only in the context of underlying genetic susceptibility. Identification of genomic loci containing these heritable risk factors has been slowed by the rarity and late onset of PBC, which has made difficult the collection of sufficient numbers of patients and family members for meaningful genetic analyses. Advancements in our ability to catalog the genetic variation in large numbers of individuals at a genome-wide scale, coupled with unprecedented efforts to recruit PBC patients for genetic study, positions us to generate data that could fundamentally change our understanding of PBC and lead to clinical innovation. Indeed, the first genome-wide association study for PBC has been published, in which multiple genes involved with IL12 signaling, a pathway that is being targeted in treatment of other inflammatory conditions, were implicated in disease. However, this study was relatively small in the genome-wide milieu and a significantly expanded effort will be necessary to truly elucidate the genetic architecture of PBC. Moving ahead, cooperation between the groups collecting biospecimens and generating genome-wide data from large numbers of patients with PBC will be essential, not only to increase power for fine mapping and future studies of rare variants and epistasis; but to streamline efforts to perform functional validation of novel discoveries. Here we provide a brief update of the current state of genetics in PBC to form a basis for understanding the considerable progress that is likely to be made in the coming years.

SUBMITTER: Juran BD

PROVIDER: S-EPMC2956841 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Update on the genetics and genomics of PBC.

Juran Brian D BD Lazaridis Konstantinos N KN

Journal of autoimmunity 20100716 3

Despite recent progress, the pathogenic mechanisms governing PBC development, treatment response and outcome remain unknown. This deficiency is in large part due to the complex nature of PBC, wherein various environmental factors may be capable of prompting disease, but only in the context of underlying genetic susceptibility. Identification of genomic loci containing these heritable risk factors has been slowed by the rarity and late onset of PBC, which has made difficult the collection of suff ...[more]

PMID: 20638243

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Project description:Stroke genetics includes several topics of clinical interest, including (1) molecular genetic variations affecting risk of monogenic stroke syndromes; (2) molecular genetic variations affecting risk of common stroke syndromes, sometimes with specific effects on risk of specific main types of stroke or subtypes of ischemic and hemorrhagic stroke; (3) genetics of conditions associated with stroke risk e.g. white matter hyperintensities, atrial fibrillation and hypertension; (4) hereditary causes of familial aggregation of stroke; (5) epigenetic impact on protein expression during acute brain injury; (6) genetic influence on stroke recovery; and (7) pharmacogenetics. Genetic research methods include candidate gene studies; Genome Wide Association Studies; family studies; RNA and protein analyses; and advanced computer-aided analytical methods to detect statistically significant associations. Several methods that could improve our knowledge of stroke genetics are being developed e.g.: Exome content analysis; Next-generation sequencing; Whole genome sequencing; and Epigenetics. During 2012-2014, several Single Nucleotide Polymorphisms (SNPs) have been related to common ischemic stroke risk. Certain SNPs have been associated with risk of specific ischemic stroke subtypes such as large vessel disease and cardiac embolism, particular subtypes of intracerebral hemorrhage (ICH), especially lobar ICH, and with prognosis after ICH. Large international studies on stroke recovery and exome content are ongoing. Advanced mathematical models have been used to study how several SNPs can act together and increase stroke risk burden. Such efforts require large numbers of patients and controls, which is achieved by co-operation in large international consortia such as the International Stroke Genetics Consortium. This overview includes an introduction to genetics, stroke genetics in general, and different genetic variations that may influence stroke risk. It presents some of the latest reports on stroke genetics published in high impact journals. The role of pharmacogenetics, the current clinical situation, and future prospects will also be discussed.

Dataset Information

Update on the genetics and genomics of PBC.

Publications

Update on the genetics and genomics of PBC.

Similar Datasets

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