Scientists have discovered an ultra-rare indigenous gene variant responsible for red hair in a few Indians, identifying 21 novel variants of the Melanocortin 1 Receptor (MC1R) gene across 91 distinct population sets in the country. The study, published in the July issue of HGG Advances, focused on the MC1R gene, a fundamental protein regulating skin and hair colour in mammals.
Key Discovery: Ultra-Rare Pathogenic Variant
The researchers identified a pathogenic variant named c.872C>A that causes the red hair colour (RHC) phenotype in an Indian child. They screened the complete coding region of MC1R in 11,021 individuals representing 91 distinct Indian populations, uncovering 9 novel and 12 ultra-rare variants.
“We analysed MC1R and identified an ultra-rare pathogenic variant, christened c.872C>A, that is responsible for the RHC phenotype in an Indian child. Further, we screened the complete coding region of MC1R in a total of 11,021 individuals, representing 91 distinct Indian populations across India, and found a total of 9 novel and 12 ultra-rare variants,” the researchers said.
Origin of the Study: A Five-Year-Old Girl
The study began after scientists learned about a five-year-old girl from a village in southern India who had red hair on her scalp, body, and eyebrows, while retaining dark brown-black eyes. The gene variant responsible for RHC had been inherited by the girl; her sister had black hair.
“Although RHC is found in 1–2 percent of the world population, its frequency varies greatly among populations of different ethnicities. However, in India, the RHC phenotype is extremely rare,” the researchers observed. “Additionally, India has a diverse range of complexion tones, from pale to wheatish, brown and dark brown, across various ethnic populations.”
Collaborative Research Effort
The study involved experts from multiple institutions, including the Centre for Cellular and Molecular Biology (Hyderabad), Tata Institute for Genetics and Society (Bengaluru), Institute of Genomics and Integrative Biology (New Delhi), Academy of Scientific and Innovative Research (Ghaziabad), Anna University (Chennai), Centre for DNA Fingerprinting and Diagnostics (Hyderabad), Indian Institute of Science (Bengaluru), Manipal Academy of Higher Education (Manipal), Banaras Hindu University (Varanasi), National Institute of Mental Health and Neurosciences (Bengaluru), and SRM Institute of Science and Technology (Kattankulathur).
Functional Validation and Population Distribution
The researchers functionally validated the ultra-rare MC1R variants as potential causes of the RHC phenotype in Indians. The distribution of some variants differed significantly among Indian populations. One variant was significantly associated with lighter skin pigmentation in the Bodh population inhabiting Ladakh.
“Our study identifies and functionally validates ultra-rare MC1R variants as potential causes of RHC phenotype in Indians. The distribution of some of these variants differed significantly among Indian populations. One of them is significantly associated with lighter skin pigmentation in the Bodh population inhabited in Ladakh,” the researchers said.
Diversity of Skin Pigmentation in India
The study also observed a diversity of skin pigmentation among Indians, ranging from light to dark complexion. Generally, Dravidian speakers from Southern India have a dark complexion. In contrast, Indo-European speakers from northern India, genetically close to Middle Easterners, Central Asians, and Europeans, have lighter skin pigmentation. Similarly, Tibeto-Burman speakers from Himalayan and north-eastern states also have lighter skin pigmentation than south Indian populations.
