Research

Sher Ali

M. Sc.
Aligarh Muslim University, India

Ph. D.
University of Delhi, India

Postdoctoral Research

  • Department of Human Genetics, Ruhr University, Bochum, Germany (2008)
  • Alexander Von Humboldt Fellow at the Max Planck Institute of Immunobiology, Freiburg, Germany (1984-1986, 2000-2001).
  • Department of Genetics, University of Leicester, Leicester, England, UK (1997)
  • Department of Anatomy and Cell Biology, Georgetown University Medical Center, Washington DC, USA (1995)
  • Department of Genetic Epidemiology, University of Utah, Salt Lake City, Utah, USA (1991)
  • Research Fellow, Beckman Research Institute of City of Hope National Medical Center, Duarte, California, USA (1986-88).
  • Postdoctoral Fellow, Department of Zoology, University of Delhi, Delhi, India (1981-1983)

Email
alisher@nii.res.in

 

Research Interest

Genome Analysis, Molecular Genetics of Human and Animal Systems, Germline Genetics, Gene Regulation and Expression, Genomics of Endangered Species, Comparative and Toxicogenomics, DNA Diagnostics, Cancer Genetics

Group Members

Dr. Deepali Pathak, Dr. Monal Sharma, Dr. Suchitra Kamle, Anju Kumari, Sandeep Kumar Yadav, Md. Qudratullah, Leena Rawal, Mr. Khem Singh Negi.

Summary of Research

Our main theme of research has been genome analysis of human and animal systems encompassing structural, functional and comparative genomics. In the context of male infertility, we demonstrated that infertility in the human males having normal spermiogram is caused due to aberrations of the several Y chromosome linked genes and loci including DYZ1 region. We analyzed 64 STSs, studied different Y-linked genes and loci and conducted single nucleotide variant (SNV) analyses in 31 infertile males with normal spermiogram along with 67 normal fertile males (NFMs) to gain an insight into the organization of their Y chromosome. Further, employing quantitative real-time PCR (qPCR), we studied copy number variation of DYZ1 arrays and three genes and mutational status of SRY by direct sequence analyses. STS analyses of the AZFa, b and c regions in these patients showed known and new mutations. Further, copies of DAZ and BPY2 in the patients were found to be affected (pv0:001) compared to those in NFMs. All the patients had normal copy number of the SRY however its sequences (in silico) showed mutations in eight patients. In four of these eight patients, SRY mutations resulted into truncated proteins. Similarly, DYZ1 analysis showed micro-deletions and it’s much reduced copy number (pv0:001) as compared to those in NFMs. Present study in males with unexplained infertility revealed deletions similar to those observed in oligospermic and azoospermic patients. Thus, there are some common but still unknown factors underlying infertility in these patients irrespective of their spermatogenic status. This work is envisaged to augment DNA diagnosis, proving beneficial in the context of in vitro fertilization (IVF) and genetic counseling.

In the context of genomics of brain tumors, we studied expression of KIT and MN1 genes and owing to gender bias, analyzed Y chromosome linked loci and genes in the male patients of Gliomas and Meningiomas. Receptor tyrosine kinase (RTK) encoded by proto-oncogene KIT is known to be involved in different types of cancers. Reportedly, KIT expression has been associated with higher grade of gliomas. Initial RT-PCR based KIT expression observed in low grade glioma cases evoked our interest to ascertain its status in glioma patients who underwent resection during 2008–2009. Contrary to earlier reports, over expression of the RTK was observed in 32.5% glioma cases across low/high grades (n=40). Using quantitative PCR (qPCR), an up-regulation of the receptor (KIT) and its ligand (KITLG) was detected in most of the immunopositive cases at the transcript level. Sequence analysis of KIT showed two nucleotide substitutions in exons 10 and 17, in 4 and 2 cases, respectively though their pathological significance remained unclear. qPCR detected gene amplification in 2/13 glioma and allele loss in 1/13 glioma cases. This was in accordance with FISH results of these KIT positive neoplastic tissues. The data suggest that deranged expression of KIT is independent of gene amplification (p>0.05). Aberrant KIT expression is significantly associated with transcriptional up-regulation (pb0.001), though the precise mechanism(s) for transcriptional activation remain unclear.

Gene isolation and characterization is not only a favorite indulgence to understand genetics but it also enriches our understanding towards organization and evolution of the genome of interest.  We pursued genomics of buffalo employing minisatellite associated sequence amplification (MASA) using cDNA rom different somatic tissues and spermatozoa and testis and oligo primers specific to VNTR loci or minisatellites. Earlier, we used oligos based on consensus of 33.6, 33.15, GACA and GATA repeats to uncover repeat tagged mRNA transcripts from the somatic tissues, gonads and spermatozoa of Bubalus bubalis. Following this, we used (GGAA)5 and (TGG)5  oligos to conduct MASA with cDNA from different tissues of water buffalo B. bubalis to detect uncharacterized transcriptomes. This led to the identification of tissue specific transcripts and in the process several candidate genes were characterized and in the process, genes having clinical significance were identified. A comprehensive knowledge of repeat tagged transcriptome is envisaged to augment our understanding on genomics in general and focused genetic roles of a gene in particular. Also such information is useful for addressing the vital issues related to the areas of biomedical genetics in human and animal biotechnology thus bridging the gap of functional and comparative genomics.

Awards / Fellowships

  • Fellow, J. C. Bose, Department of Science & Technology, New Delhi, India
  • INSA/DFG Exchange Visiting Fellowship, Ruhr University, Bochum, Germany.
  • Fellow, Indian National Science Academy
  • Fellow, National Academy of Sciences, India.
  • Fellow, Indian Academy of Sciences.
  • Life Member, Society of Biological Chemists (India). 
  • Member, International Society of Animal Genetics (I.S.A.G.), Iowa, U.S.A. 
  • Life Member, Indian Academy of Forensic Sciences. 
  • Alexander Von Humboldt Stiftung Fellowship, Bonn, Germany, 1984
  • Royal Society Fellowship from Indian National Science Academy, New Delhi and Royal Society, London to work in the laboratory of Professor Sir Alec John Jeffreys, University of Leicester, Leicester UK, September – November, 1997.
  • Fulbright Travel Fellowship (1991), United States Educational Foundation in India (USEFI).
  • INDO-US Science and Technology Fellowship jointly awarded by DST (Govt. of India) and United States Agency for International Development (USAID), January to December 1994.
  • UNESCO/TWAS Short Term Research Fellowship to work on Human Genome at University of Utah, Department of Genetic Epidemiology, Salt Lake City, Utah, USA. July 7, 1991 to October 4, (1991).
  • Alexander Von Humboldt Stiftung Fellowship, Bonn, Germany (Re-visit), November 1, 2000- March 1, 2001.
  • N.K. Iyengar Memorial Gold Medal awarded by Indian Academy of Forensic Sciences, Calcutta in Forensic Science Forum, 87th Indian Science Congress, Pune, January 4, 2000.  
  • Zahoor Qasim Gold Medal for the year 1999 awarded by the Society of Biosciences, India.
  • Young Muslim Scientist Award, MAAS, Aligarh. 1996.

Selected Publications

  • Kumari A, Yadav SK, Ali S (2012) Organizational and functional status of the Y-linked genes and loci in the infertile patients having normal spermiogram. PLoS One  7:e41488.
  • Saini M, Jha AN, Abrari A, Ali S (2012) Expression of proto-oncogene KIT is up regulated in subset of human meningiomas. BMC Cancer 12: 212.
  • Rawal L, Ali S, Ali S (2012)  Molecular mining of GGAA tagged transcripts and their expression in water buffalo Bubalus bubalis. Gene 492: 290-5.
  • Kumar S, Gupta R, Kumar S, Ali S (2011) Molecular mining of alleles in water buffalo Bubalus bubalis and characterization of the TSPY1 & COL6A1 genes. PLoS One  6:e24958.
  • Pathak D, Ali S (2011) RsaI repetitive DNA in Buffalo Bubalus bubalis representing retrotransposons, conserved in bovids, are part of the functional genes. BMC Genomics 12: 338.
  • Ali S, Ali S (2010) Genetic Integrity of the human Y chromosome exposed to groundwater arsenic. BMC Medical Genomics 3: 35-46.
  • Srivastava J, Premi S, Kumar S, Ali S (2009) Expressional dynamics of minisatellite 33.15 tagged spermatozoal transcriptome in Bubalus bubalis BMC Genomics 10: 303-311.        
  • Premi S, Srivastava J, Chandy SP, Ali S (2009)Unique Signatures of the Natural Background Radiation on the Human Y chromosomes from Kerala (INDIA). PLoS One  4: e4541.
  • Premi S, Srivastava J, Panneer G, Ali S (2008) Startling Mosaicism of the Y-Chromosome and Tandem Duplication of the SRY and DAZ Genes in Patients with Turner Syndrome. Plos One 3: e3796.
  • Srivastava J, Premi S, Kumar S, Ali S (2008) Organization and differential expression of the GACA/GATA tagged somatic and spermatozoal transcriptomes in Buffalo Bubalus bubalis. BMC Genomics 9:132 -148.

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