From the minutes: Dr MacIntyre's report on our February 2009 meeting

The President welcomed around 50 members and guests and introduced the speaker, Professor Thomas Bourgeron from the Department of Human Genetics and Cognitive Science at Institut Pasteur in Paris. His title of “How far do genes contribute to behaviour” reflects his work in the genetics of neurodevelopment, particularly in relation to autism.

Is there a genetic influence on cognitive function? – yes. The more detailed questions are whether specific genes can be identified influencing specific functions such as language or social interaction, and whether differences in these genes explain behavioural differences. He thought the answer to both questions probably yes. The background to his work is the increasing understanding of the human genome with around 22,000 genes and associated “junk” DNA, the transcription from DNA to protein, and the variable expression of this DNA in different cells in the body. Variations in the DNA are mainly related to Single Nucleotide Polymorphism (SNP) or Copy Number Variation (CNV) where a larger section of DNA is duplicated or deleted. In humans the bulk of the genome is constant – one SNP variability in between 300 and 1200 base pairs. Primates exhibit much more polymorphism. This perhaps reflects the relatively “recent” move of homo sapiens out of Africa with a limited gene pool. One aspect of this work allows identification of which common gene mutations are relatively recent and which date further back in the evolutionary timescale. Some mutations are very common in the population and some much less so. In general the former probably represent low risk mutation and the latter more likely to have high risk to the individual.

Work on autism recognises that it is a spectrum ranging from individual characteristic to full blown disease – we can assess ourselves by looking up the autism spectrum quotient. The work of Professor Bourgeron and his colleagues is exploring the genetic variability that underlies this, looking at CNVs and SNPs in patient groups, mainly from Sweden and France. This work has resulted in identification of many candidate genes and polymorphisms for autism risk. This highlights the general danger of extrapolating predictions from specific gene findings as can occur with the availability of personal genome mapping. He identified five questions which should be applied to any genetic finding – mouse or man?, pilot study or replicated?, frequency and therefore likely impact?, disease specific or found in a range of conditions?, and is it supported by clinical or functional findings?

There is however a developing understanding of what might be going on in autism. Synaptogenesis is the gradual development of neuronal connections increasing from birth through childhood with a decline in adolescence and stability thereafter. Work arising from a number of family groups with autism spectrum has shown defects in proteins involved in creating or stabilising these synaptic connections – specifically neurolipin 4 and neurexan. A mouse model has been created – knock out for neurolipin 4. They appear normal in all respects other than aspects of social interaction. We were persuaded that this included their singing performance with a reduced motivation to vocalise! This may therefore represent a general mechanism for the development of autism influenced by different genetic defects.

Another area of genetic interest relates sleep pattern to autism. Melatonin levels are known to be diminished and it transpires that some autistic patients are deficient in an enzyme involved in melatonin synthesis from serotonin. Melatonin treatment can restore normal sleep patterns in some situations. All this work begins to allow models of understanding of the possible sequences from genetics through biochemistry to functional state. More work is probably needed in identifying different phenotypes in a condition such as autism before trying to link these to particular genetic susceptibilities. The picture is complex, the possible interpretations multiple, and prospects of specific therapies still distant. However Professor Bourgeron is one of an international group of enthusiasts producing rapid progress in this area.

Following a period of question and discussion, Dr MacIntyre expressed the thanks of the Society to Professor Bourgeron for a talk which had covered a complex subject in such a fascinating and stimulating way.