Genetic finding paves way for controversial autism testing

[Guest guest]

http://www.theglobeandmail.com/news/national/autism-caused-by-wide-array-of-rare\

-gene-changes-study/article1597861/

Genetic finding paves way for controversial autism testing

Carolyn Abraham

Toronto — From Thursday's Globe and Mail

Published on Wednesday, Jun. 09, 2010 1:08PM EDT

Last updated on Wednesday, Jun. 09, 2010 11:53PM EDT

An international effort led by Canadian scientists has uncovered the complex

genetic architecture of autism, revealing brand new targets for treatment and

making it possible to predict with a DNA test at birth, or even before, about 10

per cent of those who will develop the condition.

But precisely how or when people should have access to such a test could prove

to be nearly as tricky as the disorder itself, now seen as the most common

serious developmental condition of childhood.

After sifting through the DNA of 1,500 families, members of the Autism Genome

Project, a consortium of 120 researchers in 11 countries, have made the humbling

discovery that the genetic risk factors for autism are different for each person

who suffers from it.

" I highly doubt you will find two families with the same combination of genetic

variants, " said study leader Scherer, senior scientist at the Hospital

for Sick Children in Toronto.

Autism encompasses a spectrum of lifelong neurological disorders that can vary

widely in severity and symptoms. Researchers agree an early diagnostic test

could be crucial to countering the condition's worst effects, but also

acknowledge it could be used in family planning, or as a prenatal test in which

parents may opt to terminate a pregnancy.

Researchers however caution it is too early to use a genome scan to routinely

diagnose autism until they can figure out how the genetic glitches they have

discovered play out in real life. Their paper, released Wednesday in an online

edition of Nature, says that the roots of autism involve dozens of genes fouled

up by long stretches of missing or duplicated pieces of DNA. But which genes and

which stretches differ from person to person.

To learn more about the genetic quirks they have found, Dr. Scherer, director of

the Centre for Applied Genomics, has received $8-million from the Ontario

government to run a DNA scan on nearly every child diagnosed with autism in the

province over the next three years, expected to be more than 5,000 children.

Researchers in the United States and Britain have similar plans, all of it with

an eye to developing diagnostic tests.

But in the direct-to-consumer age, the market rarely waits for more research.

Dr. Scherer expects people will be able to buy a mail-order genetic test that

scans for autism-related genes in the near future – even if the information they

can glean from it is dubious at best.

" I get e-mails from U.S. companies every month, start-ups and diagnostic

companies, looking for markers for autism, " he said, noting the findings for

this study are not protected by patent.

In this study, approximately 10 per cent of the 1,000 people with autism tested

had mutations in genes known to disrupt brain function. For this reason, Dr.

Scherer believes certain variations within these genes are predictive of an

autism disorder.

Still, if families came for testing now, " in the majority of cases we won't be

able to tell them anything, " he said. What's more, the results from such tests

can be so nuanced they ought to be delivered by a genetic counsellor, he added.

" In many ways delivering the information is in and of itself a science. "

Study co-author Szatmari, director of the Offord Centre for Child Studies

at McMaster Children's Hospital in Hamilton, said the prospect of a commercial

test " makes me nervous. I don't think we have the science yet to nail it down. …

This isn't one gene, but a profile of genes, a pattern of susceptibility, not

cause. "

Autism spectrum disorders (ASD) strike one in every 110 children. Some suffer

such severe cognitive impairment they're unable to speak. Others are savants.

Most show a preference for rigid routines and repetitive behaviours. But common

to all are social deficits that hamper the ability to interact with others.

Currently, children generally aren't diagnosed until age 4 or 5, after a battery

of psychological tests. A genetic test could allow parents to intervene with

behavioural therapies in infancy. It could also shed light on their chances of

having another child with autism, and their children's chances of having an

affected child.

Bond, a single mother of two in ford, Ont., waited years to learn

both her children had autism spectrum disorders. When a developmental specialist

tried to assess her younger son when he was three, he refused to

co-operate. Ms. Bond was told to bring him back in six months. Her son, now 14,

was 6 when he was diagnosed.

" It was a nightmare for me, constantly going to doctors, " she said. " Now they

realize the quicker we get to these kids the better. … There's that critical

time between the ages of 2 and 5. "

A genetic test, she said, could also tell parents about the specific problems

their child is likely to encounter. As part of the study, Ms. Bond learned her

son has a region of chromosome 16 deleted, which helps to explain why he also

has trouble with his spine, walking and swallowing.

" Now we know this chromosome affects so many systems, " she said. " Hopefully

someday parents will be able to hear when their child has autism that he might

need a speech therapist, but also a heart specialist. "

Ms. Bond's eldest child , now 17, was diagnosed at 12 with Asperger

syndrome, a high-functioning form of autism characterized by normal

intelligence, striking talents and obsessive interests (in 's case,

dinosaur teeth). But she does not carry the same genetic mutation as her younger

brother.

Some experts believe the increased prevalence reflects better detection and the

trend to diagnose autism over other developmental disorders. Others suspect

environmental triggers, such as toxins or food allergies. But no one doubts the

major role genes play, or that environmental forces influence them. Autism

disorders run in families, and if one identical twin develops an ASD the chances

are as high as 92 per cent the other twin will as well.

For some people at the mild end of the autism spectrum, and their advocates, who

see their unusual traits as characteristics that enrich society, the notion of

screening for autism is highly controversial.

Dr. Szatmari said the genetic research is not geared " to eradicate the disorder,

to get rid of it, but to ease the suffering earlier, when the brain is

developing, and give [children] the skills to cope as they grow up. "

Still, he acknowledged the findings " can have big effects on family planning. "

Scientists used the latest microchip tools to scan the DNA of nearly 1,000

people with autism and 1,200 controls. Such scans are not designed to pick up

specific mutations, but rather cover the whole genome and highlight areas where

large chunks of DNA are deleted or repeated like a record skipping.

These types of hiccup mutations are known as copy-number variants, or CNVs.

Researchers found that people with autism have more CNVs in their genes than

controls.

In all, the study, spearheaded by post-doctoral research fellow Dalila Pinto at

Sick Kids, identified more than 100 genes affected in the people with autism,

many of them forming part of a network that governs how brain cells grow and

talk to each other.

Some of these genes include those that overlap other forms of intellectual

disabilities and certain drugs already exist to treat them.

But where researchers expected to find that a common set of CNVs would explain

autism disorders, they instead found unique patterns of CNVs in each case. Most

had been inherited, but some are new mutations that sprung up during conception.

Researchers are now investigating whether the age of the parents increases the

risk of these glitches.

Dr. Scherer said these types of mutations are rare because people with autism do

not tend to have children who will go on to spread it through a population. In

cases where one parent has passed down a CNV, it may be that something in the

environment has transformed it from a mild trait to full blown autism. Or, he

said, it could be another inherited trait has combined to result in the

disorder.

Scientists suspect the genetic pattern found in autism, similar to the model

uncovered in schizophrenia, will also be detected in most other

neuro-psychiatric conditions.