Projects
My laboratory is interested in the study of mobile element related genetic variation. The Alu family of mobile elements comprise approximately 10% of primate genomes and are responsible for a number of different genetic disorders (see our recent reviews on mobile elements see Batzer and Deininger, 2002; Callinan and Batzer 2006; Deininger and Batzer, 2002: Deininger et al., 2003). These elements are one type of L1 element dependent retrotransposon that is specific to the Primate order. A third composite retrotransposon termed SVA is restricted to hominids and also dependent on L1 elements for mobilization (Wang et al., 2005). Collectively these retrotransposons make up a significant proportion of primate genomes both in terms of copy number and overall mass. Mobile elements play a significant role in the generation of genomic diversity through a variety of processes such as insertional mutagenesis (reviewed in Deininger and Batzer 1999; Batzer and Deininger 2002), transduction (Xing et al., 2006), recombination (Sen et al., 2006) and double strand break repair (Sen et al., 2007).
Initial research on retrotransposable elements demonstrated that, although these elements exist at a very high copy number, individual subfamilies of the elements of different genetic ages exist within the genome. Members of the recently integrated Alu, L1 and SVA subfamilies are restricted to specific parts of the primate lineage including human lineage specific elements (reviewed in Batzer and Deininger 2002). Many of these "young" mobile elements have inserted so recently within the primate lineage that individuals can be polymorphic for the presence or absence of a mobile element at a particular chromosomal location. Mobile element insertion polymorphisms offer two important advantages over other nuclear based polymorphisms for population genetics and phylogenetic studies (reviewed in Ray et al., 2006). First, the presence of a mobile element insertion represents identity by descent, since the probability that two different young mobile elements would integrate independently in the same chromosomal location is negligible. Second, the ancestral state of each mobile element insertion polymorphism is known to be the absence of the mobile element, which can be used to unambiguously root trees. The insertion of mobile elements into the genome represents a novel class of nuclear markers for the study of population genetics and phylogenetic relationships.
The research within our laboratory is focused around the characterization of mobile element based genetic variation. There are currently four major research foci within the laboratory.
Genomic Impact and Human Population Genetics
We are interested in determining the diverse roles that mobile elements have played in shaping the architecture of mammalian genomes. Currently we are in the process of identifying and characterizing new mobile elements throughout the primate order (Han et al., 2005, 2007; RMGSAC 2007; Wang et al., 2005) and in other mammals (Gentles et al., 2007; Gu et al., 2007; Mikkelsen et al. 2007) to gain insight into the amplification dynamics and impact of these elements in various genomes. We have focused on the impact that mobile elements have had upon genomic diversity through the creation of deletions during mobilization (Callinan et al., 2005; Han et al., 2005), their involvement in recombination (Sen et al., 2006), and in double strand break repair (Morrish et al., 2002; Sen et al., 2007). We are also studying the role that these elements play in the generation of genes and gene families through transduction (Xing et al., 2006; RMGSAC 2007) and how they contribute to the creation of new regulatory networks (Cordaux et al., 2006; Genetles et al., 2007; Mikkelsen et al., 2007). We are also determining the levels of human genomic variation associated with mobile elements that are unique to the human lineage in collaboration with Drs. Lynn Jorde, Mike Bamshad, Alan Rogers and Henry Harpending at the University of Utah (Bamshad et al., 2003;Rogers et al., 2007; Watkins et al., 2003; Witherspoon et al., 2006, 2007). A tree of human population relationships derived from the analysis of 100 Alu insertion polymorphisms is shown in the adjacent figure. In addition, we are interested in determining the impact that new mobile element insertions have upon the accumulation of other types of genetic diversity, and how gene conversion between mobile elements alters levels of single nucleotide polymorphism within the human genome (Roy Engel et al., 2002; Salem et al., 2003b; Vincent et al., 2003).
Primate Phylogenetic Relationships
We are utilizing a combination of computational approaches and PCR based assays to identify and characterize lineage specific Alu and L1 insertions in the Primate order in collaboration with Drs. Lynn Jorde (University of Utah), Oliver Ryder (San Diego Wild Animal Park), Todd Disotell (New York University) and Caro-Beth Stewart (SUNY-Albany). Because of the known direction of polarity of mobile element insertions and absence insertion of homoplasy (across short evolutionary distances) these elements are a novel source of genetic variation for the study of primate phylogenetic relationships (Ray et al., 2006). We are in the process of determining the phylogenetic relationships between species throughout the primate order using mobile element insertion polymorphisms (Herke et al., 2007; Ray and Batzer, 2005; Salem et al., 2003c; Xing et al., 2003, 2005, 2007). A tree of Hominid phylogenetic relationships derived from the analysis of mobile elements is shown in the adjacent figure.
Human Molecular Genetics
In these projects we are trying to characterize the genetic basis of healthy aging in humans in collaboration with Drs. S. Michal Jazwinski, Donald Scott, Joseph Su, David Welsch (LSU Health Sciences Center) Katie Cherry and Bob Wood (LSU) Eric Ravussin (Pennington Biomedical Research Center) and John Mountz (University of Alabama in Birmingham). As part of a multidisciplinary study of human longevity we are using a variety to approaches to characterize variants of genes that have previously been implicated in aging within model organisms to determine if some of these variants are associated with longevity in the Louisiana population. We are also interested in determining the levels of genetic variation within the Acadian population of Louisiana in collaboration with Drs. Bronya Keats (LSU Health Sciences Center), Mark Stoneking and Manfred Kayser (Max Planck Institute for Evolutionary Anthropology), and Prescott Deininger (Tulane University Health Sciences Center). These studies involve the analysis of genetic disorders that are unique or found at a higher frequency in the Acadian population (e.g. Acadian Ushers Syndrome see the adjacent figure) and population genetics of the Acadians as outlined above (Kayser et al., 2002, 2003; Romualdi et al., 2002; Savas et al., 2002; 2004).
Forensic Genomics
In these projects we are developing a variety of mobile element based assays for the detection of trace quantities of DNA in collaboration with Drs. Sudhir Sinha and Anthony Carter (ReliaGene, Inc.). These assays are useful in determining the source(s) of genetic material contained within complex (mixed) samples (Walker et al., 2003a, 2004, 2005). In addition, the assays are extremely sensitive when combined with quantitative PCR based analysis because of the high copy number of the interspersed elements within each genome. We have also developed new approaches for human DNA quantitation, and gender identification using mobile element insertions as shown in the adjacent figure (Hedges et al., 2003; Walker et al., 2003b). In addition, we are developing and testing new microfabricated devices for high-throughput DNA sequencing, genotyping and PCR that are low cost in collaboration with Drs. Steve Soper, Michael Murphy, Robin McCarley and others at Louisiana State University.
