- Email: [email protected]
Genes and behaviural phenotypes
are made to characterize the cognitive and beha+
A activity has a role to play in ensfypes comprises discussion
incorporated into the definition of phenotypes.
as of cognitive processing and social interaction, that is consistently associated with, and specific to, a syndrome with a chromosomal orgenetic aetiology in which there is little doubt that the phenotype is a result of the underlying condition. The equivalence between behavioural and physical phenotypes is by no means exact. First, behavioural phenotypes are difficult to measure; there are no instruments in psychology or psychiatry as precise as anthropometry or enzyme assays. For instance, the validity of a concept such as ‘cocktail party’ speech (vacuous but superficially fluent), as is alleged to be found in Williams syndrome, has never been established scientifically. Behaviours that are claimed to be characteristically phenotypical are frequently confounded by the low intellectual abilitios associated with syndromes such as Down syndrome, Angelman syndrome, Frader-Willi syndrome, Fragile X syndrome or Rett syndrome. Second, not all individuals with the syndrome have the behaviour in question. For example, a substantial minority of those with the Prader-Willi syndrome, diagnosed cytogenetically or by molecular techniques, are not hyperphagic, yet this behavioural symptom is often cited as being one of the most characteristic of the condition. Additionally, there may be considerable overlap or genetic heterogeneity, in behavioural abnormalities between syndromes.
link between gene, neurobiology, brain function and behaviour may be ~~i~minated by a study of this nature? Most attempts to discover specific genetic inferences upon behaviour and cognitive development currentiy use linkage or association studies. In mendelian traits, linkage is inferred from the
nature, a brief but competent review of ‘the new enetics’ together with accounts of a s with alleged be~av~o~ral ph Aicardi syndrome to the emitimental retardation syndrome. The most thought-provoking discussion is by Jonathan Flint, who puts the research area into perspective. olecular dissection of a behavioural phenotype may be an effective way of studying the pathway that leads from genotype to phenotype, but in our present state of knowledge this is merely a theoretical possibility. Sk
of eliavioural
complex traits, suchas psychiatric disorders, using chromosomal exclusion y contrast, association studies aim to find links between a marker and a disease in a population. Their strength lies in their power to detect genes of very small effect; but they are most successful when the marker either has a direct influence upon the phenotype (e.g. debrisoquine hydroxylase gene polymorphism in Parkinson’s disease),
or if it is so close to the susceptibility allele that it is in strong linkage disequilibrium with it. In addition to those genes the variability of which will lead to disease states, there must be many others that are essential for the development of normal cerebral structure and function. They will not be detected by linkage or association studies, but they could be detected by a study of behavioural phenotypes. Perhaps the best recent example, which provoked headlines around the world, was the investigation of a family in Holland in which male members over several generations had exhibited violent and unpredictable behaviour. The gene was presumptively X-linked
Copyright 01996 Elsevier Science Ltd. All rights reserved. 1357 - 43 10/96/$1S.(KI
PII: S 1357-4310(96)60009-4
iUlcl GWll
SciencesUnit. SIKd
Q)IXlOilci
Hospital Universilyof London, 30 GuilfordStreet.
e-
A activity has a role to play in ensfypes comprises discussion
incorporated into the definition of phenotypes.
as of cognitive processing and social interaction, that is consistently associated with, and specific to, a syndrome with a chromosomal orgenetic aetiology in which there is little doubt that the phenotype is a result of the underlying condition. The equivalence between behavioural and physical phenotypes is by no means exact. First, behavioural phenotypes are difficult to measure; there are no instruments in psychology or psychiatry as precise as anthropometry or enzyme assays. For instance, the validity of a concept such as ‘cocktail party’ speech (vacuous but superficially fluent), as is alleged to be found in Williams syndrome, has never been established scientifically. Behaviours that are claimed to be characteristically phenotypical are frequently confounded by the low intellectual abilitios associated with syndromes such as Down syndrome, Angelman syndrome, Frader-Willi syndrome, Fragile X syndrome or Rett syndrome. Second, not all individuals with the syndrome have the behaviour in question. For example, a substantial minority of those with the Prader-Willi syndrome, diagnosed cytogenetically or by molecular techniques, are not hyperphagic, yet this behavioural symptom is often cited as being one of the most characteristic of the condition. Additionally, there may be considerable overlap or genetic heterogeneity, in behavioural abnormalities between syndromes.
link between gene, neurobiology, brain function and behaviour may be ~~i~minated by a study of this nature? Most attempts to discover specific genetic inferences upon behaviour and cognitive development currentiy use linkage or association studies. In mendelian traits, linkage is inferred from the
nature, a brief but competent review of ‘the new enetics’ together with accounts of a s with alleged be~av~o~ral ph Aicardi syndrome to the emitimental retardation syndrome. The most thought-provoking discussion is by Jonathan Flint, who puts the research area into perspective. olecular dissection of a behavioural phenotype may be an effective way of studying the pathway that leads from genotype to phenotype, but in our present state of knowledge this is merely a theoretical possibility. Sk
of eliavioural
complex traits, suchas psychiatric disorders, using chromosomal exclusion y contrast, association studies aim to find links between a marker and a disease in a population. Their strength lies in their power to detect genes of very small effect; but they are most successful when the marker either has a direct influence upon the phenotype (e.g. debrisoquine hydroxylase gene polymorphism in Parkinson’s disease),
or if it is so close to the susceptibility allele that it is in strong linkage disequilibrium with it. In addition to those genes the variability of which will lead to disease states, there must be many others that are essential for the development of normal cerebral structure and function. They will not be detected by linkage or association studies, but they could be detected by a study of behavioural phenotypes. Perhaps the best recent example, which provoked headlines around the world, was the investigation of a family in Holland in which male members over several generations had exhibited violent and unpredictable behaviour. The gene was presumptively X-linked
Copyright 01996 Elsevier Science Ltd. All rights reserved. 1357 - 43 10/96/$1S.(KI
PII: S 1357-4310(96)60009-4
iUlcl GWll
SciencesUnit. SIKd
Q)IXlOilci
Hospital Universilyof London, 30 GuilfordStreet.
e-