Internal Research Groups

Wholemount insitu hybridization of FoxD3 expression, a transcription factor required to pattern developing nervous system, including neural crest lineages (E11.5 mouse embryo). Image provided by Dr P.Mill

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Medical and Developmental Genetics (MDG)

The work of scientists in the MDG Section is aimed at understanding gene function through a study of genetic mutations in humans and in model organisms, in particular mice and zebrafish.

 

PROFESSOR DAVID FITZPATRICK

PROFESSOR IAN JACKSON
Joint Heads of Medical and Developmental Genetics



 

Our Work

Our major aim is to understand the role of genes in disease and in normal development and tissue maintenance. Several groups are headed by clinically active clinician scientists. They study a range of human malformations, for example of the brain; face and limbs; both congenital eye diseases and later onset retinal anomalies leading to blindness; diseases of innate immunity; colon cancer and many other common diseases. The interests of the nonclinical groups strongly overlap and extend these themes, focussing on how genes function to control embryonic development and differentiation in multiple organ systems including kidney, heart, nervous system, eye, and limb. Others study the genetics of Mutations in Ribonuclease H2 cause innate immune-mediated inflammation in the brain. structure of the catalytic subunit showing the G37S mutation (red) in close proximity to the catalytic site (green) and substrate binding residues (blue). Nat Genet 38:910. Image provided by Dr A.Jacksoninnate immunity in mice, the function of pigment-synthesising cells in mice and fish, and the genetic links between development and cancer. There is a strong emphasis on using animal models to elucidate gene function, and we move from human genes to the model organisms but aim to translate the findings in animals back to patients. Two groups in MDG are also part of the Edinburgh Cancer Research Centre. Wherever possible our studies use specialised cultured cells rather than whole animals. Computational approaches also play a key role in analysis of gene function.

 

Embryonic mouse kidney in organ culture showing the epithelial marker E-cadherin (green) and mesenchymal/podocyte marker Wt1 (red). Image provided by R. Berry Some examples of our work:

The FitzPatrick group has identified genes causing cleft palate through studies in patients with chromosomal breakpoints. Two different genes, SATB2 and SOX9, were disrupted by breaks in regulatory regions some way outside each gene. This pinpointed long range regulatory elements whose role has been verified using cell culture as well as transgenic mice. In contrast the Hill group found an important genomic region for limb development some distance from the sonic hedgehog (Shh) gene in mice. They were able to show that the conserved element in this region was also found in humans and in the celebrated six-toed Hemingway cats, where small DNA sequence changes result in very similar defects. One component of the Wright group’s work involves genome-wide DNA analysis in isolated populations (from small islands off the Croatian and Scottish coasts), to identify genes associated with common later onset diseases. They showed that the cell membrane transporter gene SLC2A9 plays a key role in predisposing to gout.