Non-B DNA conformations, genomic rearrangements and disease

The nucleic acids encode the blueprints that coordinate all biological processes required for the survival and reproduction of living organisms. Although the number of sequenced genomes has increased significantly in recent years, the sequencing efforts have not uncovered the multiple levels of information hidden beyond the primary sequence of nucleotides. Both DNA and RNA are known to form complex intra-molecular secondary and tertiary structures that regulate diverse cellular functions (e.g., replication and transcription). However, the dynamic nature of the different types of genomes remains poorly understood.

Our main objective is to understand how such high-order DNA and RNA structures are formed in vitro and what is their role in genome organization, instability and evolution. We mainly focus on two models systems: mitochondrial and viral genomes. In particular, animal mtDNA and RNA viruses have in common a high mutation rate, short genomes, large number of available sequences and frequent genomic rearrangements.

We implement a multidisciplinary approach that integrates several predictive methods, dynamic simulations and inter-species comparisons. Our aims are: a) identify and validate new genomic structures; b) test the hypothesis that secondary structures are inherently mutation prone and thus related with genetic diseases; c) dissect the molecular mechanisms of structure-induced genomic rearrangements and d) develop molecular methods for clinical diagnosis based on patterns of structural conservation.

Related Publications


Hjelm BE, Rollins B, Morgan L, Sequeira A, Mamdani F, Pereira F, Damas J, Webb MG, Weber MD, Schatzberg AF, Barchas JD, Lee FS, Akil H, Watson SJ, Myers RM, Chao EC, Kimonis V, Thompson PM, Bunney WE, Vawter MP
Splice-Break: exploiting an RNA-seq splice junction algorithm to discover mitochondrial DNA deletion breakpoints and analyses of psychiatric disorders
Nucleic acids research. 2019. 47.10: e59-e59, DOI: 10.1093/nar/gkz164

Carneiro J, Resende A, Pereira F
The HIV oligonucleotide database (HIVoligoDB)
Database. 2017. 1. DOI:10.1093/database/bax005

Carneiro J, Pereira F
EbolaID: An Online Database of Informative Genomic Regions for Ebola Identification and Treatment
PLOS Neglected Tropical Diseases. 2016. 10(7): e0004757. DOI: 10.1371/journal.pntd.0004757

Belmonte FR, Martin JL, Frescura K, Damas J, Pereira F, Tarnopolsky MA, Kaufman BA
Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions
Scientific Reports. 2016. 28(6):25186. DOI: 10.1038/srep25186

Dong DW, Pereira F, Barrett SP, Kolesar JE, Cao K, Damas J, Yatsunyk LA, Johnson FB, Kaufman BA.
Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints.
BMC Genomics. 2014. 15(1): 677. DOI:10.1186/1471-2164-15-677

Damas J, Carneiro J, Amorim A, Pereira F.
MitoBreak: The mitochondrial DNA breakpoints database.
Nucleic Acids Research. 2014. 42 (D1): D1261-D1268 doi:10.1093/nar/gkt982

Damas J, Samuels DC, Carneiro J, Amorim A, Pereira F.
Mitochondrial DNA rearrangements in health and disease – a comprehensive study.
Human mutation. 2014. 35(1):1-14. doi: 10.1002/humu.22452

Damas J, Carneiro J, Gonçalves J, Stewart JB, Samuels DC, Amorim A, Pereira F.
Mitochondrial DNA deletions are associated with non-B DNA conformations.
Nucleic Acids Research. 2012. 40 (16): 7606-7621.

Pereira F, Soares P, Carneiro J, Pereira L, Richards M, Samuels DC, Amorim A.
Evidence for variable selective pressures at a large secondary structure of the human mitochondrial DNA control region.
Molecular Biology and Evolution. 2008. 25:2759–2770.

Pereira F, Amorim A.
Evolution: Viruses.
In: Maloy S and Hughes K (ed.) Brenners Encyclopedia of Genetics, 2013, vol. 2, pp. 566-568. Elsevier: New York