Genetics and SLI

Genetic influences on specific language impairment Dorothy Bishop University of Oxford

SLI runs in familiesRates of language/learning difficulties higherin relatives of those with SLI, compared withcontrols of similar background SLI control 50 40 % affected 30 relatives 20 10 0 Neils, Bishop, Tallal, Tomblin, 1986 1986 1989 1989

Twin Study MethodMonozygotic (MZ) twins:genetically identical Dizygotic or non-identical(DZ) twins: For genes that vary between people, have identical version for 50%

Twins growing up together• Twins usually share lots of influences: e.g. how much TV they watch, how much parents talk to them, who is caregiver in early years, diet, family income, etc.• These environmental influences will make twins similar to one another. If they are important, twins should resemble one another, regardless of whether MZ or DZ.• If genetic influences are important, MZ twins should be similar to one another, because they are genetically the same. DZ twins have 50% genes in common, so will resemble each other, but less so than MZ.

Study of twins growing up together Diagnosis in co-twins of probands with specific speech/language impairment (SSLI) Yellow area shows SSLI low language speech therapy mental the proportion of twin handicap pairs where both twins had SLI. This is greater for MZ than DZ. White area shows proportion where one twin had SLI and the other had no difficulties: much greater for DZ than MZ: n = 63 DZ: n = 27 MZ.Bishop, D. V. M., North, T., & Donlan, C. (1995). Genetic basis of specific languageimpairment: evidence from a twin study. Developmental Medicine and ChildNeurology, 37, 56-71.

A family tree that suggested there was a ‘gene for SLI’ Grandparents Parents Children Black = Speech/language impairment If you have an affected parent, you have 50% chance of having SLI KE familyHurst, J. A., Baraitser, M., Auger, E., Graham, F., & Norell, S. (1990). An extendedfamily with a dominantly inherited speech disorder. Developmental Medicine and ChildNeurology, 32, 352-355.

Finding the gene• FOXP2: gene on chromosome 7q31: Found a change in a single DNA base in affected individuals• The DNA change in the KE family is very unusual. Studies of the general population show that most people have the same DNA sequence.• The change in the KE family is a “missense mutation” – the DNA sequence change alters how the gene operates, so that it won’t be able to produce as much protein as it normally doesFisher, S. E. (2005). Dissection of molecular mechanisms underlying speech andlanguage disorders. Applied Psycholinguistics, 26, 111-128.

But KE family - not typical SLI• Case of FOXP2 led to expectation that we might find clearcut genetic mutations to explain all severe language impairments• Many other cases of SLI tested: very rare to find any mutation of FOXP2• Most language impairments behave like “complex multifactorial disorders”

Complex multifactorial disordersAggregate but do not segregate in families – i.e. run in families but you can’t trace effect of gene through the generations according to classic Mendelian geneticsMany common medical conditionsbehave this way, e.g. allergies, asthma,high blood pressure, diabetes 9

Idea of underlying continuum LowSeveral genes, each with a small effect, combine with environmental risks to influenceobserved behaviour across the whole range High 10

Tracking down genes associated with SLI• Compare language scores of people with different genotypes• E.g. study by Newbury et al (2009) found two genes on chromosome 16 associated with poor phonological short-term memory (NWR score) in a language-impaired sample Very different from FOXP2. ‘Risk’ alleles common in general population and have small effect size Gene 1: CMIP Gene 2: ATPTC2 Newbury, D., et al. (2009). CMIP and ATP2C2 modulate phonological short-term 11 memory in language impairment. American Journal of Human Genetics, 85, 264-272

Same gene often associated with many different disorders CNTNAP2 gene – downstream target of FOXP2 Common variants of the gene associated with: • Autism • Specific Language Impairment • Dyslexia • ADHD • Schizophrenia • Age at language acquisition in general population N.B. Effect sizes are SMALL. Not useful for genetic screeningKang, C., & Drayna, D. (2011). Genetics of speech and language disorders.Annual Review of Genomics and Human Genetics, 12, 145-164.

Why so much variation?• An analogy: tuberous sclerosis – the same mutation can lead to major brain malformation or minor problems with skin• Genes associated with language impairment likely to affect very early neural development• Precise impact may depend on which neuronal areas affected, which may depend on: 1. Other genes (effects may be interactive) 2. Environmental factors 3. Random effects See: http://wiringthebrain.blogspot.co.uk/2012/06/probabilistic-inheritance-and.html13

Genetics: common misconceptions• Genes are the NO! even in MZ twins, only thing that find different severity matter NO! genetic analysis• No point in says nothing about treating genetic effects of novel disorders environmental experience

Heritable ≠ untreatable• Because something is heritable does NOT mean it is immutable• Consider diabetes – large genetic contribution to risk, but we do not assume all diabetics must die!• We may need to introduce new environmental factors (e.g. insulin treatment) outside range of normal experience• In case of SLI, may need to devise specific interventions that circumvent or compensate for genetically-based problems 15

If a child has had bad teaching in mathematics, it is accepted that theresulting deficiency can be remedied by extra good teaching thefollowing year. But any suggestion that the childs mathematicaldeficiency might have a genetic origin is likely to be greeted withsomething approaching despair: if it is in the genes "it is written", it is"determined" and nothing can be done about it: you might as well giveup attempting to teach the child mathematics. This is perniciousrubbish on an almost astrological scale..... What did genes do to deserve their sinister juggernaut-likereputation? Why do we not make a similar bogey out of, say, nurseryeducation or confirmation classes? Why are genes thought to be somuch more fixed and inescapable in their effects than television, nuns,or books?" Richard Dawkins, The extended phenotype. 1982. Oxford: OUP.

Genetics and SLI

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