DNA mutation motifs in the genes associated with inherited
diseases

J 2017

DNA mutation motifs in the genes associated with inherited diseases

RŮŽIČKA, Michal, Petr KULHÁNEK, Lenka RADOVÁ, Andrea ČECHOVÁ, Naděžda ŠPAČKOVÁ et. al.

Basic information

Original name

DNA mutation motifs in the genes associated with inherited diseases

Authors

RŮŽIČKA, Michal (203 Czech Republic, belonging to the institution), Petr KULHÁNEK (203 Czech Republic, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Andrea ČECHOVÁ (203 Czech Republic, belonging to the institution), Naděžda ŠPAČKOVÁ (203 Czech Republic, belonging to the institution), Lenka FAJKUSOVÁ (203 Czech Republic, belonging to the institution) and Kamila RÉBLOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Plos one, San Francisco, Public Library of Science, 2017, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.766

RIV identification code

RIV/00216224:14740/17:00095121

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1371/journal.pone.0182377

UT WoS

000406768200074

Keywords in English

REPAIR PROTEIN MUTS; MISMATCH REPAIR; STRAND ASYMMETRIES; CONFORMATIONAL-CHANGES; BENDING PROPENSITY; METHYLATION; RECOGNITION; MECHANISMS; HOTSPOTS; COMPLEX

Abstract

V originále

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.

Links

GA16-11619S, research and development project

Name: Základní vlastnosti DNA mutačních coldspotů/hotspotů v genech asociovaných s dědičnými chorobami

Investor: Czech Science Foundation

LM2015085, research and development project

Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

RŮŽIČKA, Michal, Petr KULHÁNEK, Lenka RADOVÁ, Andrea ČECHOVÁ, Naděžda ŠPAČKOVÁ, Lenka FAJKUSOVÁ and Kamila RÉBLOVÁ. DNA mutation motifs in the genes associated with inherited diseases. Plos one. San Francisco: Public Library of Science, 2017, vol. 12, No 8, p. nestránkováno, 16 pp. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0182377.

@article{1394050,
   author = {Růžička, Michal and Kulhánek, Petr and Radová, Lenka and Čechová, Andrea and Špačková, Naděžda and Fajkusová, Lenka and Réblová, Kamila},
   article_location = {San Francisco},
   article_number = {8},
   doi = {http://dx.doi.org/10.1371/journal.pone.0182377},
   keywords = {REPAIR PROTEIN MUTS; MISMATCH REPAIR; STRAND ASYMMETRIES; CONFORMATIONAL-CHANGES; BENDING PROPENSITY; METHYLATION; RECOGNITION; MECHANISMS; HOTSPOTS; COMPLEX},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {DNA mutation motifs in the genes associated with inherited diseases},
   url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377},
   volume = {12},
   year = {2017}
}

TY  - JOUR
ID  - 1394050
AU  - Růžička, Michal - Kulhánek, Petr - Radová, Lenka - Čechová, Andrea - Špačková, Naděžda - Fajkusová, Lenka - Réblová, Kamila
PY  - 2017
TI  - DNA mutation motifs in the genes associated with inherited diseases
JF  - Plos one
VL  - 12
IS  - 8
SP  - nestránkováno
EP  - nestránkováno
PB  - Public Library of Science
SN  - 19326203
KW  - REPAIR PROTEIN MUTS
KW  - MISMATCH REPAIR
KW  - STRAND ASYMMETRIES
KW  - CONFORMATIONAL-CHANGES
KW  - BENDING PROPENSITY
KW  - METHYLATION
KW  - RECOGNITION
KW  - MECHANISMS
KW  - HOTSPOTS
KW  - COMPLEX
UR  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377
L2  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377
N2  - 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.
ER  -

RŮŽIČKA, Michal, Petr KULHÁNEK, Lenka RADOVÁ, Andrea ČECHOVÁ, Naděžda ŠPAČKOVÁ, Lenka FAJKUSOVÁ and Kamila RÉBLOVÁ. DNA mutation motifs in the genes associated with inherited diseases. \textit{Plos one}. San Francisco: Public Library of Science, 2017, vol.~12, No~8, p.~nestránkováno, 16 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0182377.

Detailed Information on Publication Record