The world of genetics has seen tremendous advancements over the last few decades, and a significant contribution to this progress has been made by the likes of prominent scientists such as Aravinda Chakravarti. His work has had profound implications in understanding the genomics of common and complex diseases. This news article delves into the life and scientific journey of Aravinda Chakravarti, whose rich career profile was highlighted in the 2019 issue of ‘Proceedings of the National Academy of Sciences of the United States of America’ (PNAS).

Chakravarti’s research has spanned across multiple facets of genetics, including human gene variation and its influence on diseases. His interdisciplinary approaches combining biology, statistics, and medicine have paved the way for understanding genetic variations in the human population. A profile of his work in PNAS sheds light on the impact of his groundbreaking research on personalized medicine, genetic mapping, and complex disease dissection.

One notable contribution by Chakravarti, as cited in PNAS, is the association of multiple SCN5A variant enhancers modulating cardiac gene expression and the QT interval (Kapoor A, et al., 2019). The SCN5A gene is crucial for proper heart function and any variation can result in serious heart conditions. Chakravarti’s efforts in dissecting the genetic variation in such genes have significantly advanced the cardiac health domain.

In his early work, Chakravarti, alongside PP Majumder, explored the variation in the ray and disk florets in four species of compositae, laying the foundation for understanding genetic variability within and between species (Majumder PP, Chakravarti A, 1976). He didn’t limit his foray into the world of genetics to research alone, having contributed literary works like ‘Not Everything We Eat Is Curry: A Bengali Guide to Indian Cuisine’ (Chakravarti A, Morizot DC, 1978), reflecting his multifaceted interests and cultural heritage.

In 1984, Chakravarti et al. made significant strides in understanding the nonuniform recombination within the human beta-globin gene cluster (Chakravarti A, et al., 1984). This discovery had implications in diagnosing and treating hemoglobinopathies, a group of disorders affecting red blood cells.

Another milestone in genetics was the identification of the cystic fibrosis gene through genetic analysis by Kerem B, et al. (1989) in which Chakravarti played a pivotal role. His contribution to this major breakthrough has led to better diagnosis, management, and therapeutic strategies for this life-threatening disease.

Chakravarti was also a part of the ambitious 1000 Genomes Project Consortium, which aimed to create an extensive map of genetic variation from human genomes. This comprehensive effort, published in Nature (Abecasis GR, et al., 2012), has revolutionized our understanding of human genetic diversity and its implications on health and disease.

Among his other significant research contributions, Chakravarti also investigated mutation analysis in the context of Hirschsprung disease (Angrist M, et al., 1995) and the role of a sex-dependent mutation in a RET enhancer underlying the disease risk (Emison ES, et al., 2005).

Chakravarti’s exploration with colleagues into the genetics of severe autism by examining the loss of δ-catenin function (Turner TN, et al., 2015) provided insights into the complexity of neurodevelopmental disorders.

His involvement in studies of blood pressure regulation (Ehret GB, et al., 2016) and the modulation of cardiac repolarization by genetic variants (Arking DE, et al., 2006) exemplifies his dedication to unraveling the genetic underpinnings of common cardiovascular diseases.

The DOI corresponding to Aravinda Chakravarti’s PNAS profile, which captures the essence of his rich career, is 10.1073/pnas.1906109116.

Keywords

1. Aravinda Chakravarti
2. Genetic Research
3. Human Genome Variation
4. Cardiac Gene Expression
5. Complex Disease Genetics

Chakravarti’s life’s work, documented and revered in numerous journals, is a testament to the power and potential of genetic research in shaping the future of medicine. His contributions, as narrated through these esteemed publications, have etched an indelible mark on the annals of scientific progress.

References

1. Davis, Tinsley H. “Profile of Aravinda Chakravarti.” Proceedings of the National Academy of Sciences 116.22 (2019): 10608-10610. doi: 10.1073/pnas.1906109116
2. Kapoor A., et al. (2019) “Multiple SCN5A variant enhancers modulate its cardiac gene expression and the QT interval.” Proceedings of the National Academy of Sciences 116:10636–10645. doi: 10.1073/pnas.1906109116
3. Majumder, P.P., and Chakravarti, A. (1976) “Variation in the ray and disk florets in four species of compositae.” Fibonacci Quarterly 14:97–100.
4. Chakravarti, A., et al. (1984) “Nonuniform recombination within the human beta-globin gene cluster.” American Journal of Human Genetics 36:1239–1258. PMID: 6097112
5. Kerem, B., et al. (1989) “Identification of the cystic fibrosis gene: genetic analysis.” Science 245:1073–1080. doi: 10.1126/science.2570460