Gene giant causes heart disorder
Robert Partridge (42007111)
Robert Partridge (42007111)
The human heart is a strong muscle but it goes under a lot of stress every day. Dilated cardiomyopathy (DCM) is a disorder that makes such strains much more dangerous and even lethal. DCM makes the heart weaker and eventually unable to pump enough blood.
It has been known for a while that the largest gene known t is connected to cases of DCM, but it was recently found to be a cause for many more cases (up to 27% of cases). The gene is called TTN and it makes the massive protein titin. This protein is in part of the heart that helps it contract (the sarcomere) when pumping the blood so a mutation of the gene that makes titin is likely to cause DCM. A picture of a sarcomere is shown below.
Until recently the gene that as thought to be the major cause of DCM as LMNA (5% of cases), and there is atleast 50 genes known to cause DCM including TTN. The new TTN data has only recently been researched because the TTN gene (and titin protein) are extremely huge and complex in comparison with other genes. The TTN has a massive 350 exon or protein-coding regions so it has been hard to analyze any mutations.
A modern exon capture technique was used to search for mutations, and parallel sequencing was found to be the best sequencing method. After doing this research it is thought the TTN mutation causes the titin to be unable to signal when the sarcomere has elongated too far, which is very dangerous due to cell damage.
The actual outcome of TTN mutations has many factors, including genetic make-up and environmental factors. An example might be someone with hypertension will experience greater DCM symptoms. It was sadly found that men would experience more sever DCM possible due to their generally larger hearts, so they are under greater strain and pressure. During the research into DCM TTN relationships it was found soe control patients had a TTN mutation so enviromental factors enhance these mutations or possibly these people might carry gene variants that actively suppress TTN mutations.
Diagnosing these TTN DCM relationships will help in the future as therapy methods are conceived, especially when life threatening matters in play.
McNally, EM (2012), 'Genetics: Broken giant linked to heart failure', Nature, vol.483, pp 281-282. online edition link: http://cf5pm8sz2l.search.serialssolutions.com/OpenURL_local?sid=Entrez:PubMed&id=pmid:22422258
MedlinePlus, 2012, 'Dilated Cardiomyopathy, viewed 16th March 2012, http://www.nlm.nih.gov/medlineplus/ency/article/000168.htm
GeneDX, 2010. Dilated Cardiomyopathy and its genetics, viewed 19th March 2012. http://www.genedx.com/site/dilated-cardiomyopathy-genetic-testing