Toward future directions to uncover the genomic factors affecting congenital disorders

Tamar Harel, M.D., Ph.D. Department of Genetics and Metabolic Disease

Presently, we lack complete knowledge of rare genetic diseases, especially congenital disorders of development. An example of such genetic disorders is Mendelian disorders that -although they are individually rare-collectively, they are common. In fact, more than 20-30 million people in the U.S. suffer from a disease before the age of 25 and approximately eight million children are born worldwide each year with a serious genetic condition associated with high morbidity, mortality and economic burden for both pediatric and adult populations.

The most common Mendelian disorders wherein a single gene can cause a disease that is inherited according to Mendel’s laws, include sickle cell anemia, color blindness, cystic fibrosis, hemophilia, thalassemia (a blood disease causing abnormal hemoglobin leading to anemia) and phenylketonuria or PKU that, if untreated, can lead to intellectual disability, seizures, behavioral problems, and mental disorders. Unfortunately, although there has been substantial progress toward identifying the genetic basis of Mendelian phenotypes (set of genes the organism carries), the genes underlying about half of all known Mendelian phenotypes have not yet been discovered and comprise the overall contribution to the burden of human disease. Presently, it is a challenge to diagnose many Mendelian phenotypes through conventional diagnostic testing.

Dr. Tamar Harel, a senior clinical geneticist and Director of the Pediatric Genetics Service at Hadassah is focusing on gaining an understanding of the pathogenetic/biological processes leading to Mendelian disorders, with the aim of attaining potential therapeutic avenues. In fact, according to new estimates, humans carry an average of one to two mutations per person that can cause severe genetic disorders or prenatal death when two copies of the same mutation are inherited. Dr. Harel uses whole exome sequencing, a novel technique that allows the rapid detection of genetic variations underlying both recessive (two copies of a mutant gene, one copy from each parent) and dominant disease (inherited from one parent).

Dr. Harel’s investigation to identify the human genetic variant that causes rare genetic diseases would be an important breakthrough, since so many people suffer from Mendelian disorders. Dr. Harel also intends to extend these studies to decipher the genetic contribution of more complex disorders, such as epilepsy and autism spectrum disorders.

Dr. Harel is a rising star medical geneticist who is first author or co-author on many original publications in various prestigious peer-reviewed journals. She has recently completed her Medical Genetics Residency and Genetics Clinical Academic Research Fellowship at Baylor College of Medicine in Texas. She is a Board-certified clinical geneticist who has recently been the recipient of the prestigious William K. Bowes Jr. Award in Medical Genetics for 2017. This award is given in partnership with Harvard Medical School, Boston Children’s Hospital, Brigham and Women’s Hospital and Massachusetts General Hospital.

Dr. Harel represents an exciting breed of scientists with cutting-edge scientific thinking who aims at deciphering and treating the underlying genetic reasoning of rare diseases that affect many people of young age. Her groundbreaking research will pave the way to future personalized diagnostics and targeted therapeutics.