-
Je něco špatně v tomto záznamu ?
DNA mutation motifs in the genes associated with inherited diseases
M. Růžička, P. Kulhánek, L. Radová, A. Čechová, N. Špačková, L. Fajkusová, K. Réblová,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
NLK
Directory of Open Access Journals
od 2006
Free Medical Journals
od 2006
Public Library of Science (PLoS)
od 2006
PubMed Central
od 2006
Europe PubMed Central
od 2006
ProQuest Central
od 2006-12-01
Open Access Digital Library
od 2006-01-01
Open Access Digital Library
od 2006-01-01
Open Access Digital Library
od 2006-10-01
Medline Complete (EBSCOhost)
od 2008-01-01
Nursing & Allied Health Database (ProQuest)
od 2006-12-01
Health & Medicine (ProQuest)
od 2006-12-01
Public Health Database (ProQuest)
od 2006-12-01
ROAD: Directory of Open Access Scholarly Resources
od 2006
- MeSH
- DNA chemie genetika MeSH
- faktor VIII genetika MeSH
- genetická predispozice k nemoci MeSH
- konformace nukleové kyseliny MeSH
- LDL-receptory genetika MeSH
- lidé MeSH
- molekulární modely MeSH
- nukleotidové motivy MeSH
- protein CFTR genetika MeSH
- simulace molekulární dynamiky MeSH
- zárodečné mutace * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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 MutSα protein is noticeably bent.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc17030659
- 003
- CZ-PrNML
- 005
- 20171025122716.0
- 007
- ta
- 008
- 171025s2017 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1371/journal.pone.0182377 $2 doi
- 035 __
- $a (PubMed)28767725
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Růžička, Michal $u CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic. Department of Condensed Matter Physics, Faculty of Science, Masaryk University, Kotlářská 2, Brno, Czech Republic.
- 245 10
- $a DNA mutation motifs in the genes associated with inherited diseases / $c M. Růžička, P. Kulhánek, L. Radová, A. Čechová, N. Špačková, L. Fajkusová, K. Réblová,
- 520 9_
- $a 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 MutSα protein is noticeably bent.
- 650 _2
- $a protein CFTR $x genetika $7 D019005
- 650 _2
- $a DNA $x chemie $x genetika $7 D004247
- 650 _2
- $a faktor VIII $x genetika $7 D005169
- 650 _2
- $a genetická predispozice k nemoci $7 D020022
- 650 12
- $a zárodečné mutace $7 D018095
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a molekulární modely $7 D008958
- 650 _2
- $a simulace molekulární dynamiky $7 D056004
- 650 _2
- $a konformace nukleové kyseliny $7 D009690
- 650 _2
- $a nukleotidové motivy $7 D059372
- 650 _2
- $a LDL-receptory $x genetika $7 D011973
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Kulhánek, Petr $u CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, Brno, Czech Republic.
- 700 1_
- $a Radová, Lenka $u CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic.
- 700 1_
- $a Čechová, Andrea $u CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic.
- 700 1_
- $a Špačková, Naďa $u Department of Condensed Matter Physics, Faculty of Science, Masaryk University, Kotlářská 2, Brno, Czech Republic.
- 700 1_
- $a Fajkusová, Lenka $u Centre of Molecular Biology and Gene Therapy, University Hospital Brno and Masaryk University, Jihlavská 20, Brno, Czech Republic.
- 700 1_
- $a Réblová, Kamila $u CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic.
- 773 0_
- $w MED00180950 $t PloS one $x 1932-6203 $g Roč. 12, č. 8 (2017), s. e0182377
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/28767725 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20171025 $b ABA008
- 991 __
- $a 20171025122758 $b ABA008
- 999 __
- $a ok $b bmc $g 1254252 $s 991686
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 12 $c 8 $d e0182377 $e 20170802 $i 1932-6203 $m PLoS One $n PLoS One $x MED00180950
- LZP __
- $a Pubmed-20171025