Professor Nabeel Affara
Professor Affara's group has had a longstanding interest in the mapping and sequencing of the mammalian sex chromosomes. In human, this has led to refinement of the human Y chromosome map and the identification of a number of important X-Y homologous genes potentially involved in male fertility and cognitive behaviour. In the mouse, this has led to the identification of novel families of amplified genes on both sex chromosomes, uncovering a genomic conflict between the X and Y genomes. In the pig, this has led to the development of the first map of the pig Y chromosome, which provided the basis for a haplotype analysis of the porcine Y.
In recent years a major effort has been directed towards the transcriptional analysis of spermatogenesis using microarray technology, with particular reference to the role of sex-linked genes in male fertility using the human, mouse and porcine model systems. The group has established a substantial array production facility and has recently added the Illumina transcriptional profiling and SNP genotyping platform. The group has developed considerable oligounucleotide and cDNA based expression array resources for human, mouse and pig for the investigation of germ cell differentiation and mouse models of male infertility. In addition, substantial array CGH (aCGH) resources have been developed for the investigation of copy number variation, once again with a particular focus on the sex chromosomes. Transcriptional and aCGH studies have included:
- In Mouse:
- A detailed examination of the first pre-pubertal wave of spermatogenesis in mouse and various models of mouse infertility to unpick the patterns of gene expression associated with the appearance of different germ cell types.
- An array study of the female response to the presence of seminal plasma.
- A transcriptional, Western and immunochemical analysis of apoptotic pathway changes in mouse mutants where the endocrinological regulation of spermatogenesis has been disrupted.
- In Human:
- Establishment of the utility of aCGH for characterisation of Y deletions leading to male infertility and for delineating copy number variations affecting the X and Y chromosomes.
- Expression array profiling of human testicular biopsies from men with various spermatogenic pathologies.
- In Pig:
- An investigation into the genetic basis of sow aggression towards newborn offspring (a closely analogous model for the human condition puerperal psychosis). Genome scan studies have identified several QTL and our array expression analysis of hypothalamic tissue from the brains of aggressive and non-aggressive sows has highlighted a number of promising candidate genes and genetic pathways.
Recently, the group has developed collaborations with the Liggins Institute, University of Auckland, New Zealand to investigate (using genomic strategies) rat models for the Developmental Origins of Health and Disease. This is a rapidly growing area where the metabolic state of an organism is set during embryonic and foetal development through epigenetic modification of gene expression patterns in response to nutritional and environmental cues. The consequences of interaction with the postnatal nutritional environment can lead to complex disease in later life. Thus it is important to understand how epigenetic modification in early life can lead to disease and what factors influence this outcome. The group are studying the transcriptional (using microarrays) and epigenetic correlates of disease predisposing early life foetal-maternal-nutritional interactions in rat models.