Most siblings with a diagnosis of autism do not share the same genetic risk factors for the disorder and are as distinct in their behaviors as any brothers and sisters, scientists reported on Monday in a study that came as a surprise to many doctors, if not to parents.
Scientists analyzed genetic material from 85 families, using a technology called whole-genome sequencing. Unlike other approaches, which illuminate a sample of a person’s genetic material, the whole-genome technique maps out the entire voluminous recipe, every biological typo, every misplaced comma or transposed letter. Each of the families had two children with a diagnosis of autism.
The researchers focused their analysis on about 100 genetic glitches linked to the development of autism. They found that about 30 percent of the 85 sibling pairs in the study shared the same mutation, and about 70 percent did not. The sibling pairs who shared a genetic glitch were more similar to each other, in their habits and social skills, than those pairs whose genetic risks were different, the study found.
The finding drives home the exasperating diversity of autism, even in the most closely related individuals. And it suggests that scientists will need to analyze tens of thousands of people, perhaps more, to tell any meaningful story about its biological basis.
Experts said the report, in the journal Nature Medicine, would most likely encourage changes in clinical practice. Some hospitals analyze the genetic profile of the eldest affected sibling to try to understand an infant, or to advise parents of the odds of having another child with the same disorder. That approach is not informative in most cases, the study authors said.
“This is very important work for people like me,” said Valerie South, an emergency nurse in Oakville, Ontario, outside Toronto. Her sons Cameron, 20, and Thomas, 14, have severe autism. In a family of four or more, the odds of having two children with autism is about one in 10,000.
In 1998, she and her husband consulted doctors about the risks of having another child with autism. At the time, they had Cameron and an older son, Mitchell, who has no developmental problems.
“We wanted Mitchell, who is a great brother, not to have to carry the burden all by himself,” Ms. South said. “They told us that the odds of having another Cameron were tiny. And even if it happened, they said, it wouldn’t be a severe case.”
They did not get another Cameron — or another Mitchell. They got Thomas, who shares Cameron’s autism diagnosis, but who is very different. Thomas will walk right up to strangers, Ms. South said, while Cameron draws back. Thomas loves his iPad, whereas Cameron has no interest in computers. Thomas is an “escape artist,” continually on the move, while Cameron prefers to park himself in one place.
The new study provides a good biological explanation for those differences — and should put to rest the sort of predictions the Souths got before having Thomas.
“This study makes us step back and realize we’re not necessarily going to get as much predictive value out of genetic mapping as we thought,” said Helen Tager-Flusberg, a developmental neuroscientist at Boston University, who was not involved in the research.
The report is the latest twist in a genetic plot that seems only to thicken. In recent years, scientists have isolated gene mutations that steeply raise the risk of autism. But those glitches account for only a tiny fraction of cases, and the number of them continues to increase — to about 100 now, and counting.
Scientists have not been able to tell a coherent story about causation. It could be that common variants — that is, gene variations that many people carry, which cause no apparent problems — increase the dormant possibility for the disorder, in some combinations.
The investigation focused on 85 families with two children on the autism spectrum. “We anticipated that, more often than not, there would be shared inheritance” in siblings, said the project’s research director, Dr. Stephen Scherer, a professor of medicine at the University of Toronto. Dr. Scherer is also director of the Center for Applied Genomics at the Hospital for Sick Children. “That wasn’t the case.”
Experts not involved in the study said the finding was convincing and important. “The study is very well designed, the end result is somewhat surprising, and it reiterates the complexity of the underlying genetics of autism,” said Dr. Yong-hui Jiang, an associate professor in the department of pediatrics and neurobiology at the Duke University School of Medicine.
The report is the first major finding from a large-scale collaboration financed by Autism Speaks, an advocacy group, and based at the University of Toronto and the Hospital for Sick Children. The researchers are analyzing genetic material from a registry of more than 2,800 families who have at least one child with a diagnosis. The registry, funded by both the National Institutes of Health and Autism Speaks and managed by Autism Speaks, includes comprehensive medical and behavioral histories and is the largest of its kind.
In a first, the study coordinators, working with Google, published the data and analysis tools online, in a cloud-based format available to any user. In previous genetic studies, it has typically taken researchers months or years to make their data available, if they do so at all, Dr. Scherer said. Autism specialists said that the study findings were a welcome confirmation of a common observation. “After you get over the surprise and think about it, we all know that the kids are different in these families,” Dr. Tager-Flusberg said.
The ratio of siblings with autism who have a common genetic basis for the disorder versus those who do not — now 30 percent to 70 percent — may be less lopsided as researchers analyze more such families, some experts said. The study “used a quite liberal approach for variants relevant to autism, and the finding, while solid, may be less general than implied,” said Dr. David B. Goldstein, director of the Institute for Genomic Medicine at Columbia University.
Most mosquito bites occur at night but some mosquitoes reach out for blood even during the day. Fortunately, malaria alleviation moved a step forward, last year, with the World Health Organisation reporting a reduction in deaths by half, but what does this mean for sub-Saharan Africa, the most affected region?
When insecticide-treated nets are used properly by three-quarters of the people in a community, malaria transmission is cut by 50 per cent, child deaths are reduced by 20 per cent, and the mosquito population drops by as much as 90 per cent.
Statics also indicate that 90 per cent of all malaria deaths occur in sub-Saharan Africa and malaria costs an estimated $12 billion in lost productivity in Africa.
It is estimated still that only 5 per cent of children in sub-Saharan Africa currently sleep under insecticide-treated net. But how is the situation like in Rwanda?
A rise in malaria cases
The Minister for Health, Dr Agnes Binagwaho, blamed the current rise in malaria incidences on substandard bed nets supplied by Netprotect.
Netprotect is a Danish company that was hired on an estimated $15 million to supply over three million nets in 2013 only for it to supply substandard nets.
“Now three million mosquito nets currently in use within the country are less efficient because they do not have enough medicine to kill mosquitoes,” Dr Binagwaho said.
This is unfortunate considering that malaria contributes about 24 per cent of the total global death burden.
However, recommendations suggest eradication of malaria to be handled in a holistic manner, and that users should know that proper usage is much more effective than how defective a net is, because even a bad net will not let in mosquitos unless it torn or misused.
Mosquito insecticide-treated nets have long been used in the fight against mosquito bites, and have been shown to give substantial protection against malaria, but no room to guarantee effectiveness hence calling for a set of operational procedures to be followed by everyone.
Kibagabaga Hospital director Osee Sebatunzi advises that for nets to be effective, they should be re-treated promptly depending on the instructions and a user should properly deploy it around the bed each night before going to sleep.
According to Dr Sebatunzi, the use of mosquito nets should be accompanied by similar preventative strategies like erosion of stagnant water, slashing bushes around the house, disposing off cans and containers that are likely to harbor mosquitoes.
“Old, torn nets are dangerous to individuals and should be disposed of while the more people in a given community utilise nets the safer it becomes for everyone to fight against malaria,” Dr Sebatunzi adds.
“All mosquito nets should be kept in good condition by the user.”
Torn, treated and untreated bed nets
In similar studies done by WHO, it is revealed that using untreated bed nets in good condition is associated with a significantly lower prevalence of malaria (51 per cent protection).
The findings suggest that an untreated net, provided that it is in relatively good condition, can protect against malaria, although points out that untreated nets do not constitute a good intervention: just a single small hole is enough to render the net useless.
This means that others in the same room or shelter are not protected, and may receive more mosquito bites.
Focus by the ministry is to ensure that malaria cases go down up to zero. The intervention strategies are many but for effective control of malaria, the public should play an important role as well.
Dr Tekle Gebre Egziabher, a gynaecologist at Rwanda Military Hospital, Kanombe, says expectant mothers should attend and as well follow advice given in their antenatal clinics.
“Antenatal clinics provider are meant to guide and provide information concerning several measures that also include malaria prevention strategies such as the operation of bed nets,” Dr Egziabher says.
“Failure to follow the guidelines on malaria prevention causes the disease to remain a threat in expectant individuals and more so likely to cause complications such as, pulmonary oedema, renal failure, foetal loss, celebral palsy in the foetus among so many others such as miscarriages.”
Minister Dr Binagwaho urged Rwandans to continue using the nets as government looks into ways to have them replaced to minimise risks of being infected. After distributing 900,000 thousand nets, the ministry will distribute two million more nets next month.
Parliamentarian Anita Mutesi has urged people of Burera to tackle the problem of stunting since its effecst on a child are irreversible.
She made the call on Thursday during an outreach visit intending at raising awareness on nutrition and the 1000 days campaign launched by the ministry of health since 2013.
According to the demographic health survey (DHS) conducted in 2010, Burera scored 52% in terms of stunting, which is the disproportion of the age of a child and his weight and height.
Malnutrition and stunting persist in Burera despite the district being one 0f the main bread baskets in the country, mainly for Irish potatoes.
According to the district’s health director Jacques Bizima, the number of chronic malnourished children dropped from 142 at the beginning of the year to 73 at present.
He explained that the high level of malnutrition in Burera is due to the fact that while many people are involved in agriculture, they pay little attention to education and balanced nutrition of their children.
In addition, when teenage girls give birth they often leave the baby with their grandmother while they move elsewhere to look for work. There is also a problem of poor family planning that leaves families unable to take proper care of their children.
Aimee Naganze, an officer in charge of health promotion at the Rwanda Biomedical Center, remarked that families should be the main force in tackling nutritional problems. She further stressed that the prevention of stunting starts during the pregnancy as the health of a pregnant woman can affect the development of the child.
However, Naganze stated that the father also has an important role to play in ensuring the health of the future child by taking care of his wife during pregnancy.