Blood: gene mutation of aplastic anemia

September 29, 2014 / Biovalley / recently, an international scientific team found a mutant gene that causes aplastic anemia Aplastic anemia is a serious blood disease, which causes the bone marrow to not produce normal blood cells The researchers studied a family with hereditary blood disease, which has three generations of blood disease The researchers found a defect in a gene regulating telomere and chromosome structure in the family, which plays a key role in the function of normal cells "Identifying the cause of this genetic defect may help future molecular dependent therapies that bypass genetic defects and restore bone marrow to make blood cells." Dr Hakon Hakonarson said Hakonarson and his colleagues, working with Australian scientists, published the article online September 9 in the journal blood "We are very happy that this discovery can help us understand the causal relationship between some gene mutations and some specific diseases." Said Dr Tracy Bryan The team studied an Australian family with genes for aplastic anemia and leukemia Dr Hakonarson and Yiran Guo followed the genomics experts from BGI Shenzhen to sequence the whole exome DNA of the family, and identified the genetic mutation gene of a chronic disease anemia This genetic mutation encodes telomere binding protein tpp1 Telomere is a complex structure of DNA and protein, it is located at the end of chromosome, they maintain the stability of chromosome They are sometimes compared to the plastic head at the end of the laces to prevent them from wearing Telomeres shorten after each cell division, which gradually loses their protective effect Aging cells have shorter telomeres, which makes DNA damage and cell death more and more likely In addition to the aging process, some genetic and acquired disorders may shorten telomeres, hinder the speed of bone marrow hematopoiesis and lead to bone marrow failure, which is an example of aplastic anemia Bryan's team studied the function of the mutant gene for chronic anemia They found that the mutation shortened telomeres and disrupted their ability to attract telomerase, which is too short to protect cells In the current study, researchers have shown that mutations in the gene of chronic disease anemia alter telomere binding protein tpp1 and disrupt the interaction between telomere and telomerase Without telomerase to help maintain telomere function, blood cells lose their structural integrity and die quickly, which can lead to bone marrow failure and aplastic anemia It has not been found that other genes have some effects on bone marrow failure before Now, the research will add the gene of chronic disease anemia to the list, and find that the gene has pathogenic effect for the first time "This understanding of the improved underlying molecular mechanisms may provide a new way to treat diseases such as aplastic anemia," Hakonarson said "For example, researchers may find other ways to supplement telomerase to telomere, so that telomere can restore its protective effect." This article is the original compilation of Biovalley, welcome to reprint! Please indicate the source of the reprint and attach the original link thank you! doi:10.1182/blood-2014-08-596445 PMC: PMID:
Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1 Yiran Guo1, Melissa Kartawinata2, Jiankang Li3, Hilda A Pickett4, Juliana Teo5, Tatjana Kilo5, Pasquale M Barbaro2, Brendan Keating6, Yulan Chen3, Lifeng Tian1, Ahmad Al-Odaib7, Roger R Reddel2, John Christodoulou8, Xun Xu3, Hakon Hakonarson1, and Tracy M Bryan2, *
Abstract Telomerase is a ribonucleoprotein enzyme that is necessary for overcoming telomere shortening in human germ and stem cells Mutations in telomerase or other telomere-maintenance proteins can lead to diseases characterized by depletion of hematopoietic stem cells and bone marrow failure Telomerase localization to telomeres requires an interaction with a region on the surface of the telomere-binding protein TPP1 known as the TEL patch Here we identify a family with aplastic anemia and other related hematopoietic disorders, in which a one amino acid deletion in the TEL patch of TPP1 (ΔK170) segregates with disease All family members carrying this mutation, but not those with wild-type TPP1, have short telomeres When introduced into 293T cells, TPP1 with the ΔK170 mutation is able to localize to telomeres but fails to recruit telomerase to telomeres, supporting a causal relationship between this TPP1 mutation and bone marrow disorders ACD/TPP1 is thus a newly-identified telomere-related gene in which mutations cause aplastic anemia and related bone marrow failure disorders.