Svetlana Yatsenko, MD
Professor, Department of Pathology, Department of Obstetrics, Gynecology & Reproductive Sciences, Director of UPMC Cytogenetics Laboratory
The XX-axis and XY-axis of human health: We do research to understand the genetic differences between man and women, to define the genes that affect women development, health, and fertility, and find the ways to cure gender-specific diseases.
Svetlana Yatsenko, MD
Research in Brief
Dr. Yatsenko’s main research interests concentrate on study of molecular basis and mechanisms of genomic alterations and complex chromosomal rearrangements, as well as gene dosage effects that lead to congenital disorders, birth defects and cancer. Dr. Svetlana Yatsenko is interested in both basic and translational clinical research studies. Dr. Yatsenko has developed and utilized a high-resolution custom microarray to study alterations involving the X chromosome. Her current projects have focused on the X chromosome alterations and their contribution to disorders of sex determination, ovarian and testicular failure, fetal development, and tumor predisposition. She is also engaged in research aimed to investigate biological and technological bases for false positive and false negative findings of cell free DNA analysis in pregnant women and improve non-invasive methods for fetal genomic diagnoses.
Genetics of Pregnancy Loss
The potential RPL etiologies include endocrine and autoimmune factors; fetal and placental infections; anatomical defects; environmental, occupational, personal habits, and genetic factors . Up to 50% of patients with RPL have no clearly defined etiology. This study focuses on the investigation of genetic causes of RPL that includes recurrent chromosomal abnormalities, unbalanced chromosomal aberrations resulting from parental balanced rearrangements, parental genetic mutations affecting fetal viability or ability to carry pregnancy.
Genetic evaluation of miscarriage tissue obtained at the time of the second and subsequent pregnancy losses is recommended as a part of clinical evaluation and should be offered to all couples with two or more consecutive pregnancy losses. The combination of a genetic evaluation on miscarriage tissue with an evidence-based assessment for RPL will identify a probable or definitive cause in over 90% of miscarriages. Chromosome microarray analysis adds significantly to RPL assessment . This research study is being conducted by the University of Pittsburgh.
Unexplained Infertility: Determinants of Early Embryo Development
Almost 30% of couples with infertility carry the diagnosis of unexplained infertility. Rather than unexplained, it might be due to problems during early embryo development. In vitro fertilization (IVF) provides a unique opportunity to identify cases where the possible problem may be with the development of the embryo. We know that early on, maternal genes play a large role in embryo development, and then later on, the embryo’s own genes take over. A handful number of maternal effect genes are known, while many more genes remain to be determined. We hope to learn more about the maternal and paternal genes that may be involved in this complex process.
This study will look at couples who do not have a known cause of infertility and subsequently may or may not go through the process of in vitro fertilization (IVF). Couples who have problems with the progression of multiple embryos to the blastocyst stage and those whose treatment did not result in clinical pregnancy are eligible. This research is being conducted by the University of Pittsburgh.
Primary Ovarian Insuffiency (POI)
The goal of this research is to investigate genetics causes of primary ovarian insufficiency (POI) with or without diminished ovarian reserve (DOR) in women with normal karyotype and normal testing for premutations in the FMR1 gene.
Disorders of Sex Development (DSD) and Gonadal Dysgenesis
Disorders in sexual development are a complex group of congenital conditions where chromosomal, gonadal or anatomical sex is atypical. These conditions could exhibit a variety of phenotypes. DSD is caused by a range of genetic etiologies including chromosome abnormalities or sex chromosome mosaicism and gonadal dysgenesis in patients with normal 46,XY or 46,XX karyotype with changes in the genes, responsible for gonadal development and function. By further studying these conditions we can better understand the molecular causes of DSD. This research study is being conducted by the University of Pittsburgh.
- Yatsenko SA, Rajkovic A. Genetics of human female infertility. Biol Reprod. 2019. pii: ioz084. PMID: 31077289.
- Yatsenko SA, et al. A high-resolution X chromosome copy-number variation map in fertile females and women with primary ovarian insufficiency. Genet Med. 2019; PMID: 30948856
- Katari S, et al. Chromosomal instability in women with primary ovarian insufficiency. Hum Reprod. 2018; 33:531-538. PMID: 29425284.
- Aarabi M, et. al. Autism spectrum disorder in females with ARHGEF9 alterations and a random pattern of X chromosome inactivation. Eur J Med Genet. 2018; pii:S1769-7212(18)30285-4. PMID: 30048823.
- Aarabi M, et. al. Importance of complete phenotyping in prenatal whole exome sequencing. Hum Genet. 2018; 137(2):175-181. PMID:29392406.
- Dangle P, et al. Female-to-male sex reversal associated with unique Xp21.2 deletion disrupting genomic regulatory architecture of the dosage-sensitive sex reversal region. J Med Genet 2017; 54:705-709. PMID: 28483799.
- Tas E, et. al. Familial deletion of the HOXA gene cluster associated with hand-foot-genital syndrome and phenotypic variability. Am J Med Genet A. 2017; 173:221-224. PMID: 27649277.
- Yatsenko SA, et al. Highly heterogeneous genomic landscape of uterine leiomyomas by whole exome sequencing and genome-wide arrays. Fertil Steril. 2017;107(2):457-466.e9. PubMed PMID: 27889101.
- Yatsenko SA, et al. Maternal cell-free DNA-based screening for fetal microdeletion and the importance of careful diagnostic follow-up. Genet Med. 2015;17(10):836-8. PMID: 25569438
- Yatsenko SA, et al. Application of chromosomal microarray in the evaluation of abnormal prenatal findings. Clin Genet. 2013;84(1):47-54. PMID: 23020214.