Genomics in the Scientific Literature [15] - Chronic Disease

Genomics in the Scientific Literature
Topics in the Scientific Literature

Chronic Disease

1. Genetic Determinants of Bone Density and Fracture Risk--State of the Art and Future Directions
Duncan EL & Brown MA
J Clin Endocrinol Metab 2010 Apr

J Clin Endocrinol Metab. 2010 Apr 7. [Epub ahead of print]

Genetic Determinants of Bone Density and Fracture Risk--State of the Art and Future Directions.
Duncan EL, Brown MA.

University of Queensland Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.

Abstract
Context: Osteoporosis is a common, highly heritable condition that causes substantial morbidity and mortality, the etiopathogenesis of which is poorly understood. Genetic studies are making increasingly rapid progress in identifying the genes involved. Evidence Acquisition and Synthesis: In this review, we will summarize the current understanding of the genetics of osteoporosis based on publications from PubMed from the year 1987 onward. Conclusions: Most genes involved in osteoporosis identified to date encode components of known pathways involved in bone synthesis or resorption, but as the field progresses, new pathways are being identified. Only a small proportion of the total genetic variation involved in osteoporosis has been identified, and new approaches will be required to identify most of the remaining genes.

PMID: 20375209 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20375209?dopt=Abstract



2. Genetic kidney diseases
Hildebrandt F
Lancet 2010 Apr;375(9722):1287-95

Lancet. 2010 Apr 10;375(9722):1287-95.

Genetic kidney diseases.
Hildebrandt F.

Howard Hughes Medical Institute and Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. fhilde@umich.edu

Comment in:

Lancet. 2010 Apr 10;375(9722):1227-8.

Abstract
Knowledge of the primary cause of a disease is essential for elucidation of its mechanisms, and for adequate classification, prognosis, and treatment. Recently, the causes of many kidney diseases have been shown to be single-gene defects-eg, steroid-resistant nephrotic syndrome, which is caused by podocin mutations in about 25% of children and nearly 15% of adults with the disease. Knowledge of a disease-causing mutation in a single-gene disorder represents one of the most robust diagnostic examples of personalised medicine because the mutation conveys an almost 100% risk of developing the disease by a defined age. Whereas single-gene diseases are rare disorders, polygenic risk alleles arise in common adult-onset diseases. In this Review, I will discuss prominent renal single-gene kidney disorders, and polygenic risk alleles of common disorders. I delineate how emerging techniques of total exome capture and large-scale sequencing will assist molecular genetic diagnosis, prognosis, and specific treatment, and lead to an improved elucidation of disease mechanisms, thus enabling development of new targeted drugs. Copyright 2010 Elsevier Ltd. All rights reserved.

PMID: 20382325 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20382325?dopt=Abstract



3. Genetic studies of IgA nephropathy: past, present, and future
Kiryluk K, et al.
Pediatr Nephrol 2010 Apr

Pediatr Nephrol. 2010 Apr 13. [Epub ahead of print]

Genetic studies of IgA nephropathy: past, present, and future.
Kiryluk K, Julian BA, Wyatt RJ, Scolari F, Zhang H, Novak J, Gharavi AG.

Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, Russ Berrie Pavilion #413, New York, NY, 10032, USA.

Abstract
Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and an important cause of kidney disease in young adults. Highly variable clinical presentation and outcome of IgAN suggest that this diagnosis may encompass multiple subsets of disease that are not distinguishable by currently available clinical tools. Marked differences in disease prevalence between individuals of European, Asian, and African ancestry suggest the existence of susceptibility genes that are present at variable frequencies in these populations. Familial forms of IgAN have also been reported throughout the world but are probably underrecognized because associated urinary abnormalities are often intermittent in affected family members. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently demonstrated. Recent data indicates that these IgA1 glycosylation defects are inherited and constitute a heritable risk factor for IgAN. Because of the complex genetic architecture of IgAN, the efforts to map disease susceptibility genes have been difficult, and no causative mutations have yet been identified. Linkage-based approaches have been hindered by disease heterogeneity and lack of a reliable noninvasive diagnostic test for screening family members at risk of IgAN. Many candidate-gene association studies have been published, but most suffer from small sample size and methodological problems, and none of the results have been convincingly validated. New genomic approaches, including genome-wide association studies currently under way, offer promising tools for elucidating the genetic basis of IgAN.

PMID: 20386929 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20386929?dopt=Abstract