Sequencing of the human genome has been hailed as major scientific milestone. But obtaining an overview of the human genome and understanding its evolution, biomedical implications and future challenges are difficult, since these topics are discussed in a myriad of articles that employ very different approaches. This lecture series aims to reveal the central issues and achievements of this project. The course has its own home page at http://www.stats.ox.ac.uk/~hein/HumanGenome/. If the individual lecturers agree, their slides will be made available at this www-site before the lecture. The lecture series will be in Hilary Term 2004 and take place 2pm–4pm Tuesdays in Lecture Theatre A in Zoology, South Parks Road.
Besides sketching the background of the human genome project, this lecture will try to preview the lectures series and main conceptual components of exploiting the human genome sequence: evolution, variation, "genotype to phenotype" models, gene structure, function, modelling and genome annotation.
There has traditionally been a strong focus on coding regions as being maintained by purifying selection, but the situation is more complex: other regions are under different forms of selection and characterizing such regions their selective constraints and mode of evolution is a major challenge. Du to the large amount of comparative data, it both neutral mutation processes and selection can be characterized leading to both answers and new questions.
By comparing human genes with genes from mouse, rat and chimp, we can reveal which genes have been preserved, duplicated, deleted or pseudogenised. Moreover, we can identify those genes that are evolving rapidly, and others that are evolving slowly. This talk will focus on the slowly-evolving 'eutherian core' that characterises mammalian-, vertebrate- or eukaryotic-specific function.
Positive selection although rarer pinpoints the emergence of new functions that differentiate mammals. Evidence for adaptation is challenging to trace as often it is embedded in an ocean of neutral changes and has to be particularly marked to stand out.
Only a tiny proportion of the human genome appears to code for functional proteins. Recent years have shown that much of the RNA world is still with us and different RNAs have been discovered with a variety of functional roles. It is increasingly clear that the genome also contains a large number of genes (probably thousands) that code for functional RNAs. Such non-coding RNA genes are being discovered fast. Detecting (experimentally or computationally) transcribed RNA and functionally characterizing these is a major activity at present. Databases of such RNAs (Rfam) and comparison to other species yield exciting insights. Computational approaches to RNA gene finding are in their infancy, but recent advances have been central in key discoveries.
Understanding the population dynamics leading to present day variation at the genomic level has made population genetics central in interpreting human variation, which also underlies association mapping and human evolutionary studies. Understanding selection, mutation and recombination processes are key objectives. The major project (HapMap) of mapping human genetic variation by determining the haplotypes from individuals in multiple human populations is discussed.
Association Mapping is the focus of huge expectations presently and has great medical potential in tracing positions that responsible for disease or any specified phenotype. It is also statistically difficult and many characters might be inherently difficult to dissect using only combined phenotype, haplotype data sampled from a population.
Human Genomic Variation gives the possibility of understanding human evolution that is unprecedented. Early expansions and peopling of the globe can be traced. The history of specific genes and chromosomes tell different stories. The relationship to our closest relatives among the primates can be determined precisely determined. Ancestral population structure.If you wish to attend this lecture series, please email email@example.com. This is only to get an estimate of the number of attendants. I hope to see you there.