Byrappa VENKATESH / Sydney BRENNER   
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  Byrappa VENKATESH  
  Lab Location: #5-04

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  Key Publications  

Aparicio, al.
Whole-genome shotgun assembly and analysis of the genome of Fugu rubripesScience (2002) 297, 1301-1310.

Christoffels, A., Koh, E.G.L., Chia, J., Brenner, S., Aparicio, S. and Venkatesh, B.
Fugu genome analysis provides evidence for a whole-genome duplication early during the evolution of ray-finned fishes.
Mol. Biol. Evol. 21, 1146-1151. 2004.

Venkatesh, B., Tay, A., Dandona, N., Patil, J.G. and Brenner, S.
A compact cartilaginous fish model genome.
Curr. Biol. 15, R82-R83, 2005.

Lee, A. P., Koh, E.G.L., Tay, A., Brenner, S. and Venkatesh, B.
Highly conserved syntenic blocks at the vertebrate Hox loci and conserved regulatory elements within and outside Hox gene clusters.
Proc. Natl. Acad. Sci. USA. 103, 6994-6999, 2006.

Venkatesh, B., et al.,
Ancient noncoding elements conserved in the human genome.
Science 314, 1892. 2006.

Venkatesh, B., et al.
Survey sequencing and comparative analysis of the elephant shark (Callorhinchus milii) genome.
PLoS Biol. 5(4): e101, 2007.

Davies, W.L., Carvalho, L.S., Tay, B.H., Brenner, S., Hunt, D.M. and Venkatesh, B.
Into the blue: gene duplication and loss underlie colour vision adaptations in a deep-sea chimaera, the elephant shark Callorhinchus milii.
Genome Res. (2009) 19: 415-426.

Ravi, V., Lam, K., Tay, B-H., Tay, A., Brenner, S. and Venkatesh, B.
Elephant shark (Callorhinchus milii) provides insights into the evolution of Hox gene clusters in gnathostomes. Proc. Natl. Acad. Sci. USA. (2009). 106: 16327-16332.

Maeso, I. et al.
An ancient genomic regulatory block conserved across bilaterians and its dismantling in tetrapods by retrogene replacement.
Genome Res. (2012) 22: 642-655.

Amemiya, C.T.,,
The African coelacanth genome provides insights into tetrapod evolution.
Nature (2013) 496:311-316.

Mehta, T.K., et al.
Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum).
Proc. Natl. Acad. Sci. USA.(2013) 110: 16044-16049.

Venkatesh,B., et al.
Elephant shark genome provides unique insights into gnathostome evolution
Nature (2014) 505, 174-179.

Brawand, D., et al.
The genomic substrate for adaptive radiation in African cichlid fish.
Nature (2014) 513: 375-381.

Lin, Q. et al.
The seahorse genome and the evolution of its specialized morphology.
Nature (2016) 540: 395-399.


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Byrappa Venkatesh obtained his BSc and MSc from the University of Agricultural Sciences, Bangalore, India and PhD from the National University of Singapore. He did his postdoctoral studies under the Nobel Laureate Sydney Brenner at the Medical Research Council (MRC), Cambridge, UK and returned to Singapore in 1992 to set up this Lab. He is currently a Professor and Research Director in IMCB, an adjunct Professor of the Department of Paediatrics, National University of Singapore and a Joint Scientist at KK Women’s and Children’s Hospital. In recognition of his achievements, Venkatesh was honored with Singapore's "National Science Award" in 2004. He is a member of the Human Genome Organization (HUGO) and a Fellow of the National Academy of Agricultural Sciences, India. He is also a chairperson of the 'Genome 10K' project, an international project which aims to catalogue genomes of 10,000 vertebrates.

  Sydney BRENNER

Sydney Brenner received his DPhil from Oxford University in 1954. He was a member of the Scientific Staff of the MRC Laboratory of Molecular Biology in Cambridge, UK from 1957-1993, and served as its Director from 1979-1986. He is the recipient of many awards and honors in recognition of his contributions to molecular biology, including the Lasker Award (1971 & 2000), British Companion of Honour (1987) and the Nobel Prize for Medicine or Physiology in 2002.
  Comparative and Medical Genomics

We use a comparative genomics approach to better understand the structure, function and evolution of the human genome as well as for understanding the genetic basis of morphological diversity of vertebrates. Our projects involve sequencing and assembling whole-genomes, genome annotation, whole-genome comparisons, and identification of common and unique genetic features in different lineages. We proposed the compact genome of fugu (Takifugu rubripes) as a model vertebrate genome in 1993 (Nature 366: 265-268, 1993) and determined its whole genome sequence in 2002 (Science 297: 1301-1310, 2002). Fugu genome was the first vertebrate genome to be sequenced soon after the completion of the human genome. We identified elephant shark (Callorhinchus milii) as a model cartilaginous fish genome because of its relatively small genome size (1 Gb) and led an International Consortium that sequenced the whole-genome of elephant shark (Nature 505: 174-179, 2014). Jawless vertebrates (cyclostomes), comprising lampreys and hagfishes, are the most ancient lineage of vertebrates and hence an important reference for understanding the origin and evolution of all vertebrates. We chose the Japanese lamprey (Lethenteron japonicum), which has a smaller genome than the sea lamprey, as a model jawless vertebrate and generated a draft sequence of its genome. In addition, we were involved in sequencing and analysis of the genomes of coelacanth (a living fossil), African cichlids, mudskippers, Asian arowana, spotted gar, ocean sunfish and seahorse. Our group is also playing a lead role in “Genome 10K”, an international project which aims to sequence the genomes of 10,000 vertebrates.       

Medical Genomics
We apply our high-throughput next-generation sequencing and bioinformatics capabilities for identifying variants associated with genetic diseases. The main collaborators of our Medical Genomics projects are scientists from the Institute of Medical Biology (IMB) and the Translational Laboratory in Genetic Medicine (TLGM), and clinicians from the KK Women’s and Children’s Hospital and the National University Hospital. A major ongoing project is aimed at identifying variants associated with rare genetic diseases, whose precise diagnosis is often a challenge to clinicians due to the diagnosis odyssey of patients with uncommon symptoms. By sequencing whole-exomes of patients, their unaffected parents and other family members, we have been able to identify causative variants for more than 100 rare and undiagnosed diseases. Besides helping clinicians in the precise diagnosis of the disease and deciding appropriate therapeutic measures, these findings have improved our understanding of the functions of many human genes. The objective of another ongoing project is to identify germline and somatic mutations associated with neuroblastoma, which is the most common extracranial solid tumour in children. This project is based on sequencing and analysis of a large number of FFPE tumour and normal tissue samples collected by clinicians at the KK Women’s and Children’s Hospital over several years.


Besides sequencing and annotation of whole genomes and transcriptomes, our research interests include the role of gene and genome duplications in the evolution of vertebrate genomes; and evolution of cis-regulatory elements and its contribution to the morphological diversity of vertebrates. Prediction of conserved noncoding elements and their assay in transgenic zebrafish and mouse have proved to be an effective strategy for discovering cis-regulatory elements in the human genome, and for understanding the role of regulatory evolution in the phenotypic diversity of vertebrates.

Links to our genome browsers:

        Fugu Genome Project
        Elephant Shark Genome Project
        Japanese Lamprey Genome Project