Manir Ali

Genetics of eye disease

There are two principal strands to our research. Firstly, we study a number of genetic disorders affecting the front of the eye, including primary congenital glaucoma (see picture), microcornea, sclerocornea and anterior segment dysgenesis, in families of Pakistani origin, both in Yorkshire and in Northern Pakistan. To identify the genes and proteins involved, we carry out genetic analysis of families in which the parents are related, sequentially applying techniques for autozygosity mapping, bioinformatics, and gene sequencing. We also carry out functional characterization of the proteins identified, using methods such as reverse transcription PCR, in situ hybridisation, immunohistochemistry, siRNA and gene transfer.

In the second research strand, we study three strains of blind chickens (retinopathy globe enlarged, retinal dysplasia and degeneration and blindness enlarged globe), which arose naturally in Scottish farm stocks. To these, we apply similar genetic methods, to locate and identify the defective genes, and then search for mutations causing similar conditions in human patients. More recently, we have also explored the use of these birds as models for the study of emmetropisation, the process of coordination between eye growth and image focus.

Ali M, McKibbin M, Booth AP, Parry DA, Jain P, Riazuddin SA, Hejmancik JF, Khan SN, Firasat S, Shires M, Gilmour DF, Towns K, Murphy A-L, Jafri H, Rashid Y, Toomes C, Craig J, Mackey DA, Riazuddin S, Inglehearn CF (2009) Null mutations in LTBP2 cause Primary Congenital Glaucoma. Am J Hum Genet 84:664-671.

Ali M, Ramprasad VL, Soumittra N, Mohamed MD, Jafri H, Rashid Y, Danciger M, McKibbin M, Kumaramanickavel G, Inglehearn CF (2008) A missense mutation in the nuclear localization signal sequence of CERKL (p.R106S) causes autosomal recessive retinal degeneration. Mol Vis 14:1960-1964.