DNA mutation motifs in the genes associated with inherited diseases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00095121" target="_blank" >RIV/00216224:14740/17:00095121 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/17:00071216

Result on the web

<a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377" target="_blank" >http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0182377" target="_blank" >10.1371/journal.pone.0182377</a>

Result language

angličtina

Original language name

DNA mutation motifs in the genes associated with inherited diseases

Original language description

Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs) rarely associated with mutations (coldspots) and frequently associated with mutations (hotspots) exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutS alpha protein is noticeably bent.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Plos one

ISSN

1932-6203

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

8

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

—

UT code for WoS article

000406768200074

EID of the result in the Scopus database

—