Page 27 - Annual report 2021-22

Annual Report 2021-22 |

Mohammed Faruq

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Mohammed Faruq works on understanding of the genetic and molecular basis of neurogenetic
disorders, chiefly, hereditary ataxias.

Movement disorders that usually affects coordination, balance, and speech are called as ataxia. Some
forms of ataxia are inherited and a progressive deterioration of movement and eventually
degeneration of cerebellum is known to occur. The inheritance pattern can be autosomal dominant,
autosomal recessive, X linked or maternal inheritance via mitochondria.

Faruq’s lab is working to decipher the deeper genetic spectrum of cerebellar ataxias in Indian
population using whole exome and genome sequencing approach. To this end, patient recruitment
was started (and is ongoing) and nearly 300 patients were enrolled at AIIMS with Achal K Srivastava,
MD. He is also working on setting up of a clinically applicable targeted panel for rapid diagnosis of
ataxias and to create a reference clinical and genetic cohort for Indian ataxia cases. To achieve this,
his lab sequenced a panel of 6 common genes for identification of common and rare mutations in
ATM, SACS, SETX, TTBK2, ELOVL5, and AFG3L2. This panel was customized for rapid screening.
Generation of a biorepository of Indian ataxia patients comprising of DNA samples that can be used
for creation of iPSC lines is another major focus of his lab. Approximately 7000 DNA samples have
been registered at CSIR-IGIB so far in this biorepository. He has also been working to identify novel
ataxia associated genes using integrated functional genomics approach on patient derived cell lines.

The major type of autosomal dominant cerebellar ataxia includes spinocerebellar ataxias (SCA). The
most common SCAs are trinucleotide repeat expansion disorders. SCA2 is one of the most common
types of SCAs and the cause is expansion of CAG repeats (more than 33 repeats seen in patients of
SAC2) in the ATX2 gene. Faruq’s lab in collaboration with AIIMS, New Delhi has created a specific
cohort for SCA2 and performed Genome Wide Association Study for 96 SCA2 patients and 96 healthy
control samples (192 Samples) obtained from AIIMS, New Delhi. Axiom array genotyping was used to
identify modifiers through GWAS approach in SCA2 cohort. The analysis of haplogroup differences
between two SCA2 cohorts of different age at onset were drawn. Total 34 SNPs markers were found
significant to be included for PHASE analysis to generate haplotypes in the flanked region of CAG
repeat in the ATXN 2 gene.

In collaboration with Arvind Bagga, AIIMS, New Delhi and Pankaj Hari, AIIMS, New Delhi, his lab is
working to identify mutations and genetic variations in pediatric kidney disease. It involves working
on patients with nephritic syndrome, non-diarrheal and non-autoimmune forms of HUS and patients
with Vesico Ureteral reflex (VUR) to assess whether genetic variation is present in genes implicated in
renal fate induction, nephron formation and nephron patterning among Indian children’s pediatric
genetic disorders. Towards that end, whole exome sequencing of patient cohorts of Nephrotic
syndrome (n~250), Vesicouretric reflex (n~60) and HUS (n~50) has been performed. Using an
extensive NGS pipeline a detailed search led to the identification of variations in candidate genes of
respective disorders. Many novel and recurrent mutations were identified particularly in case of
nephritic syndrome.