Veronica van Heyningen
Veronica van Heyningen is a Section Head at the Medical Research Council's Human Genetics Unit ”“ part of the Institute of Genetics and Molecular Medicine in Edinburgh. She maintains a wide interest in genetic mechanisms and broad aspects of biology that can be gleaned from the study of human genetic disease. For the past two decades she has studied the underlying genes implicated in human developmental eye anomalies. The identification of three major developmental regulator genes: PAX6, SOX2 and OTX2, all implicated in brain as well as eye development, have led to extensive mutational studies in humans and dissection of gene function in model organisms. Detailed patient analysis led to early observations of how chromosomal breakpoints some way outside certain genes can lead to altered expression of those genes, and to the study of distant DNA elements regulating gene expression. Observing the variability and occasional absence of phenotype in cases with known pathological mutations, led us to study mechanisms of phenotype modulation and gene-environment interactions. Comparisons between different model organisms, including humans, also revealed some of the mechanisms of evolutionary change. More than 200 publications along the way have led to funding awards, invitations to participate in interesting meetings and some honours. Veronica van Heyningen was a Beit Memorial fellow immediately after finishing her PhD on early human gene mapping in Oxford under the guidance of Walter Bodmer. From 1993, she was a Howard Hughes International Research Scholar for five years, allowing her to build up her group. Since 1995 she has been an Honorary Professor at the University of Edinburgh. She was elected a Fellow of the Royal Society of Edinburgh in 1997, a member of EMBO in 2002 and a Fellow of the Royal Society in 2007. She participated in the Human Genetics Commission, which provides advice to the UK government on social and ethical issues in genetics. She is a past President of the European Society of human Genetics and current President of the Genetics Society. She continues to enjoy the fast moving science of human molecular genetics and the mentoring of young scientists entering the field, and has acquired a renewed interest in human development through her grandchildren.
New insights into the mechanisms of human disease.
Recent advances in genomic technologies are opening up new vistas in our approaches to understanding not only Mendelian single-gene anomalies, but also more common later onset diseases. The growing capacity to dissect genomic information on a large scale is revealing new mechanisms for perturbing “normal” function at every stage of life. Relatively conventional genomic analysis has uncovered unexpected features of genomic organisation including the presence of large tracts of low copy number repeats which may be associated with dynamic copy- number variation, some associated with disease. Such variation can now be routinely identified using genomic arrays. Genome analysis has also uncovered the presence of several types of non-coding RNAs whose function is now being deciphered and, in some cases being associated with abnormalities. Evolutionary sequence comparisons have revealed the prevalence of highly conserved non- coding regions of DNA and in many instances regulatory function has been assigned to these. The ability to study single nucleotide polymorphisms on a large scale in large disease cohorts and normal controls is fueling the era of genome-wide association studies, where disease-predisposing genes are uncovered and provide growing understanding of normal biology as well as deviations from the norm. About half the common disease-associated variants lie within the regulatory regions of the genome, making functional identification and validation a new and exciting challenge. Galloping increases in sequencing capacity are opening the door to whole-genome sequencing of many individuals. The capacity for generating vast quantities of sequence data is producing a strong demand for the development of novel bioinformatic approaches to data analysis. The possibility of sequencing many esoteric model organisms provides exciting insight and new tools for biology and promise for the development of therapeutic approaches.