Genetics of recombination

In mammals, recombination occurs in highly localized regions, usually 1-2 kb in size, termed hotspots. Hotspots can be positioned relatively close to each other or separated by long distances, up to several hundred kilobases.

Our lab investigates the distribution, location, sex specificity of hotspots on entire chromosomes and the influence of genetic background on their activity. We have set up four genetic crosses for large-scale mapping of recombinational activity, with 3000 offspring of female and 300 offspring of male meioses. The maps show substantial differences in crossover rates along the chromosome, with alternating regions of high and low recombination rates. Generally, female recombination rates are higher than in males in the middle section of the chromosome, whereas males show elevated recombination near telomeres.

Particularly exciting is our work on crossover interference, and its relation to the sex differences in recombination rate. Crossover interference appears to act on a physical level; when the difference in the compaction of chromosomes is taken into account, the distances between crossovers in males and females is nearly identical. We hypothesize that crossover interference, and the difference in the compaction of chromosomes in males and females, is the primary cause of the sex difference in recombination rate. (Females have longer chromosomes at meiosis, and so may exhibit more crossovers.)

W e have found evidence for the role of trans-acting genes on the activity of individual hotspots. Experiments for mapping these genes are ongoing, and several exciting avenues for investigation of mechanisms regulating recombination are available.

Currently, I am working on the Recombination database project which includes a database design, development of tools for uploading microarray data to the database and web interface to identify recombination hot spots.

My other Center projects are:
- Interface for visualization of analyzed microarray data for the Diet Strain Survey study
- Center web site redesign and maintenance

Current Position

Research Scientist - The Jackson Laboratory
Ph.D. - Molecular Biology / Genetics - 1993

Grant funded work

1 R01 GM078452 Petkov (PI) 03/2007-02/2012
Chromosome-Wide Mapping of Recombinational Activity
The goal of the proposed project is to generate the first high-resolution, large-scale map of recombination hotspots for an entire chromosome.
Role: Principal Investigator

1 R01 GM078643-01A1 Paigen K.(PI) 1/1/06-12/31/09
NIH/NHGRI Genomic Organization of Recombination Hot Spots
The major goal of this grant is obtain a detailed map at one Kb resolution of all recombinational hotspots, including their sex and haplotype specificity, for five different five Mb regions on separate chromosomes using 6000 meioses.
Role: Associate Research Scientist

1 P50 GM076468-01 Churchill (PI) 4/1/06-3/31/11
Genome Dynamics: Evolution, Organization and Function
The major goal of this grant is to create a National Systems Biology Center at the Jackson Laboratory. The center is formulated around the idea that the mammalian genome contains chromosomal domains of functionally related genes that interact non-randomly.
Roles: Project Leader, Core Leader

Previous positions

1993-1997 Major Assistant Professor, Department of Genetics, Faculty of Biology, University of Sofia "St. Kliment Ohridski"

1997-2001 Research Associate, Liver Research Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

2001-2004 Research Associate, Technology Development Department, The Jackson Laboratory, Bar Harbor, ME

Awards and Honors

1986 Magna Cum Laude, MS graduation

Professional Services

2004 Ad hoc reviewer, Trends in Biotechnology

2005 Ad hoc reviewer, Clinical Chemistry, Comparative Medicine, PloS Genetics

Peer-reviewed publications (in chronological order)

Belcheva RG, Bisserkov VI, Ilieva HL, Beshkov VA, Petkov PM. 1986. Karyological studies on Lacerta vivipara (Jacq.) collected in Bulgaria. Cytologia 51:567-570.

Belcheva RG, Petkov PM, Kehaiov IR. 1989. Cytogenetic and isoenzyme investigations on two lizard species from genus Lacerta - Lacerta vivipara Jacq. and Lacerta muralis Laur (Reptilia, Lacertidae). Acta Zoologica Bularica 37:34-42.

Petkov PM, Ralchev K, Dunkov B. 1990. Immunochemical and electrophoretic characterization of diaphorase-2" from three drosophila species. Genetics and Breeding 23:285-291.

Ralchev KH, Petkov PM, Dunkov BC. 1992. Purification and characterization of diaphorases from some Drosophila species. Biochem Genet 30:305-315.

Petkov PM, Valevska AV, Ralchev KH. 1994. Comparative characterization of the molecular weights of diaphorase-1 and diaphorase-2 from several Drosophila species. C R Acad Bulg Sci 47:69-71.

Ralchev KH, Petkov PM, Valevska AV. 1994. A new method for purification of diaphorase-1 and diaphorase-2 from Drosophila virilis and structural investigations. C R Acad Bulg Sci 47:91-93.

Dabeva MD, Laconi E, Oren R, Petkov PM, Hurston E, Shafritz DA. 1998. Liver regeneration and alpha-fetoprotein messenger RNA expression in the retrorsine model for hepatocyte transplantation. Cancer Res 58:5825-5834.

Oren R, Dabeva MD, Karnezis AN, Petkov PM, Rosencrantz R, Sandhu JP, Moss SF, Wang S, Hurston E, Laconi E, Holt PR, Thung SN, Zhu L, Shafritz DA. 1999. Role of thyroid hormone in stimulating liver repopulation in the rat by transplanted hepatocytes. Hepatology 30:903-913.

Oren R, Dabeva MD, Petkov PM, Hurston E, Laconi E, Shafritz DA. 1999. Restoration of serum albumin levels in nagase analbuminemic rats by hepatocyte transplantation. Hepatology 29:75-81.

Dabeva MD, Petkov PM, Sandhu J, Oren R, Laconi E, Hurston E, Shafritz DA. 2000. Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation into adult rat liver. Am J Pathol 156:2017-2031.

Petkov PM, Kim K, Sandhu J, Shafritz DA, Dabeva MD. 2000. Identification of differentially expressed genes in epithelial stem/progenitor cells of etal rat liver. Genomics 68:197-209.

Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA. 2001. Stem cell properties and repopulation of the rat liver by fetal liver eipithelial progenitor cells. Am J Pathol 159:1323-1334.

Petkov PM, Cassell MA, Sargent EE, Donnelly CJ, Robinson P, Crew V, Asquith S, Haar RV, Wiles MV (2004a) Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse. Genomics 83:902-11

Petkov PM, Ding Y, Cassell MA, Zhang W, Wagner G, Sargent EE, Asquith S, Crew V, Johnson KA, Robinson P, Scott VE, Wiles MV (2004b) An Efficient SNP System for Mouse Genome Scanning and Elucidating Strain Relationships. Genome Res. 14:1806-1811

Petkov PM, Zavadil J, Goetz D, Chu T, Carver R, Rogler CE, Bottinger EP, Shafritz DA, Dabeva MD. 2004. Gene expression pattern in hepatic stem/progenitor cells during rat fetal development using cDNA microarrays. Hepatology 36(3):617-627.

Kelmenson PM, Petkov P, Wang X, Higgins DC, Paigen BJ, Paigen K (2005) A torrid zone on mouse chromosome 1 containing a cluster of recombinational hotspots. Genetics 169:833-41

Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, Paigen K (2005) Evidence of a large-scale functional organization of mammalian chromosomes. PLoS Genet 1:e33

Ishimori N, Li R, Walsh KA, Korstanje R, Rollins JA, Petkov P, Pletcher MT, Wiltshire T, Donahue LR, Rosen CJ, Beamer WG, Churchill GA, Paigen B (2006) Quantitative trait loci that determine BMD in C57BL/6J and 129S1/SvImJ inbred mice. J Bone Miner Res 21:105-12

Grozdanov PN, Petkov PM, Karagyozov LK, Dabeva MD. (2006). Expression and localization of PCSK9 in rat hepatic cells. Biochem Cell Biol. 84(1):80-92.

Graber JH, Churchill GA, DiPetrillo KJ, King BL, Petkov PM, Paigen K. (2006). Patterns and mechanisms of genome organization in the mouse. J Exp Zool 305A:683-688.

Petkov PM, Broman KW, Szatkiewicz JP, Paigen K. (2007). Crossover interference underlies sex differences in recombination rates. Trends Genet 23(11):539-542.

Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, Paigen K. (2007). Evidence of large-scale functional organization of mammalian chromosomes. PLoS Biol 5(5):e127 (Correspondence).

Ng SH, Parvanov E, Petkov PM, Paigen K. (2008). A quantitative assay for crossover and noncrossover molecular evens at individual recombination hotspots in both male and female gametes. Genomics 92:204-209.

Paigen K, Szatkiewicz JP, Sawyer K, Leahy N, Parvanov ED, Ng S, Graber JH, Broman KW, Petkov PM. (2008). The recombinational anatomy of a mouse chromosome. PLoS Genet 4(7):e1000119. PMC2440539

Ng SH, Maas SA, Petkov PM, Mills KD, Paigen K. (2009) Colocalization of somatic and meiotic double strand breaks near the Myc oncogene on mouse chromosome 15. Genes Chromosomes Cancer. 48(10):925-30.

Ng SH, Madeira R, Parvanov ED, Petros LM, Petkov PM, Paigen K. (2009). Parental origin of chromosomes influences crossover activity within the Kcnq1 transcriptionally imprinted domain of Mus musculus. BMC Mol Biol. 10:43. PMCID: PMC2689222

Parvanov ED, Ng SHS, Petkov PM, Paigen K. (2009). Trans-regulation of mouse meiotic recombination hotspots by Rcr1. PLoS Biol. 7(2):e36. PMCID: PMC2642880

Books

Ralchev KH, Petkov PM, Harizanova NT, Gueorguieva TG, Dunkov BC, Ivanova PM, Modreva MM. 1997. A guide for demonstrations in gene engineering. Sofia, Bulgaria: Sofia University.

Fox, R.R., Wiles, M.V., Petkov, P.M.(2006).Genetic monitoring.In: Mouse in Biomedical Research. Fox J, Barthold S, Davisson MT, Newcomer C, Quimby F, Smith A (eds.), Elsevier Press, second ed. (in press).