Publication: A peek into retrotrotransposon-derived polymorphisms in human through the 1000 genome project data

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Title	A peek into retrotrotransposon-derived polymorphisms in human through the 1000 genome project data
Authors/Editors*	P, Liang
Where published*	FASEB Summer Research Conference: “Mobile Elements in Mammalian Genomes”
How published*	Proceedings
Year*	2009
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Abstract	Retrotransposons constitute over 40% of the human genome, and they impact the function of genome in many ways, some of which just started to be appreciated. With certain classes of retrotratransposons, particularly, Alus, L1s, and SVA, remain to be active, they contribute to an important part of genetic polymorphisms among human populations in a form of presence and absence of retrotranposon insertions, and these variations are believed to partly attribute to the phenotype differences in humans, such as disease susceptibility. So far, several thousand cases of retrotransposon insertion polymorphisms (RIPs) have been identified by us and others, with the majority of those obtained from computational comparative genomic analysis based on limited human genomic sequences. However, the actual level of such types of polymorphisms existing in human populations remains to be an intriguing puzzle. In an attempt to address this question, we have started analyzing the very recently available new human genome sequence data generated from The 1000 Genome Project undertaken by an international Consortium. Lunched in early 2008, the project has been progressing at a rapid pace and has been generating a huge amount of DNA sequence data. As of this writing, sequence data has been available for a total of 190 genomes at a total of more than 45 trillion bases in length. In this preliminary analysis, we focused on the data for a Nigeria family of three (two parents and one child), for which deep sequencing data has been available. We utilized the paired Solexa sequence reads and mapped them against the human reference genome to identify Alus, L1s, and SVAs that are present in the reference genome but not in the test genomes. We also compared such polymorphic insertions with data in the database of Retrotransposon Insertion Polymorphisms in humans (dbRIP) and classified them as known or novel RIPs. We found unexpectedly large number of novel RIPs for Alus and L1s, majority of which below to older subfamilies that are thought to be less activate, but a relatively small number of novel RIPs for SVAs. When compared the RIPs in the genome of the child with those in the genomes of her two parents, we also found a large number of new RIPs in genome of the child, many of which are expected to have resulted from de novel insertions. Despite of the need of validating these computational identified RIPs, the preliminary data does demonstrate that: 1) personal genomics data generated using the 2nd generation of sequencing technology is of great utility for identifying novel retroransposon-derived genetic variations; 2) the degree of such type of variations may be much higher than what we currently appreciate, with Alus and L1s from many old subfamilies remaining active. This research is in part supported by grants from Canada Research Chair program, Canadian Foundation of Innovation, Ontario Ministry of Research and Innovation and Brock University to PL and is facilitated by the use of SHARCNET high performance computing.

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