Scientists have successfully sequenced the genome of a baby in the womb without tapping its protective fluid sac. Maternal blood sampled at about 18 weeks into the pregnancy and a paternal saliva specimen contained enough information for the scientists to map the foetus’ DNA. This method was later repeated for another expectant couple closer to the start of their pregnancy. The researchers checked the accuracy of their genetic predictions using umbilical cord blood collected at birth.
Jacob Kitzman and Matthew Snyder, working in the laboratory of Dr. Jay Shendure, associate professor of genome sciences at the University of Washington, led the study. Kitzman is a National Science Foundation Graduate Research Fellow.
Scientists have long known that a pregnant woman’s blood plasma contains cell-free DNA from her developing foetus. Foetal DNA appears in the mother’s plasma a few weeks after conception. It rises during gestation and normally vanishes after the baby arrives. While the concentration varies among individuals, about 10 percent of the cell-free DNA in a pregnant woman’s blood plasma comes from her foetus.
Based on this phenomenon, other research labs are designing maternal blood tests for major aberrations in the foetus’s genetic makeup. The tests are considered a safer substitute for the more invasive sampling of fluid from the uterus, a common procedure in obstetrical practice. These new tests search for just a few genetic disorders or specific congenital abnormalities. For example, a test targeted for Down syndrome would look for evidence of three copies of chromosome 21.
Kitzman explained what distinguishes his team’s latest methods is the ability to assess many and more subtle variations in the foetus’ genome, down to a minute, one-letter change in the DNA code.
‘The improved resolution is like going from being able to see that two books are stuck together to being able to notice one word misspelled on a page,’ said Kitzman.
With technical advances as well as statistical modelling, the research group overcame several obstacles that had stymied previous efforts to determine foetal genomes. With a preponderance of maternal rather than foetal DNA in plasma samples, a major problem was figuring out which genetic variants had passed from mother to child. The scientists applied a recently developed technique to resolve the mother’s haplotypes, which are groups of genetic variations residing on the same chromosome. From these groupings, the researchers could pick out the parts of the baby’s genetic material inherited from each parent with over 98 percent accuracy.
‘It was rewarding to apply biostatistics to help solve this problem,’ said Snyder, who came to genome sciences from the fields of statistics and economics.
Still, he added, there is more work to be done to improve this technique. The researchers pointed to the need for a more robust, scalable, overarching protocol, as well as ways to lower costs and automate and standardise parts of the process. Washington University

One of the largest studies to investigate birth complications and later mental health has found that premature birth constitutes a single, independent risk factor for a range of severe psychiatric disorders. Researchers at King’s College London in the UK and Karolinska Institutet suggest that neurodevelopmental differences in those born prematurely may be important in understanding the link.
Researchers identified all individuals registered in the Swedish birth register between 1973 and 1985 who were alive and living in Sweden at the age of 16, a total of nearly 1.5 million individuals. By analysing national hospital discharge registers, they identified all individuals admitted to hospital with their first episode of a psychiatric disorder.
The study found that individuals born extremely prematurely (less than 32 weeks gestation) were 2.5 times more likely to have psychosis as young adults, nearly 3 times more likely to have depression, and 7.4 times more likely to have bipolar disorder than those born at term (37-41 weeks gestation). The findings also revealed a smaller, yet still significant, increased risk of developing bipolar disorder, psychosis and depression for those born moderately prematurely (32-36 weeks).
The study also investigated the link between premature birth, eating disorders and alcohol and drug dependency, but association with these disorders was much weaker. Other adverse perinatal factors including newborn health, maternal socio-demographic characteristics and maternal psychiatric history were taken into account and were found to have no significant effect on the findings.
‘We believe that the increased risk of mental disorders in those born very prematurely can be explained by alterations of brain development’, says Professor Christina Hultman at Karolinska Institutet, who led the Swedish part of the study. ‘The immature nervous system in these children is particularly vulnerable to brain injury resulting from birth complications.’
Approximately 6 percent of babies in Sweden are born prematurely every year. Thanks to research and new technology, today many of prematurely born can be saved. Most of these babies go on to lead healthy lifestyles, although as a group they are more likely to require extra school support and be hospitalised with a variety of physical problems. Therefore the authors point to the importance of raising awareness of the increased risk of mental health disorders in people born prematurely, and suggest gestational age should be considered when investigating risk factors for psychiatric disorders in young adults. Karolinska Institute

Certain proteins, such as 14-3-3, conserve their basic functions of cell cycle control in diverse organisms, from worms to humans. In a study led by Julián Cerón and Simó Schwartz Jr, researchers from the Bellvitge Biomedical Research Institute (IDIBELL) and the Research Institute of Vall d’Hebron (VHIR) respectively, have described germ line functions of par-5, which is one of the two 14-3-3 proteins existing in Caenorhabditis elegans, worms used as experimental model in genetic studies. The overexpression of the 14-3-3 proteins is related to the resistance of tumours to chemotherapy, which could have implications for clinical practice.
Researchers found that par-5 gene, as its human homologues, is required for DNA damage response in C. Elegans validating the model to investigate chemotherapies and genetic modifications since 14-3-3 proteins are therapeutic targets in cancer
The powerful genetic tools of C. elegans have allowed a precise functional dissection of the single 14-3-3 protein present in their germline. The researchers have discovered that par-5 is not only necessary for proper cell cycle regulation, but also to prevent the accumulation of endogenous DNA damage and genomic instability.
Moreover, this study reveals that par-5 is required for DNA repair response when it is damaged by chemicals or ionizing radiation. In such response, the researchers propose a model where PAR-5 regulates CDK-1 phosphorylation to stop the cell cycle and repair the damage induced by chemotherapeutic agents.
The overexpression of the 14-3-3 protein has been related to chemotherapy resistance in cancer cell lines while its downregulation sensitises cells to therapy-induced cell death. Therefore, this study in C. elegans provides the basis for a model to study chemotherapy response in the context of a whole living organism.
Regulators proteins 14-3-3, evolutionarily conserved, bind to signalling proteins and affect their stability, activity or cellular localisation. So, they are involved in the regulation of various cellular processes, including apoptosis, the cell cycle and stress response.
In addition, the researchers found that par-5 is required for cell cycle arrest in response to replicative stress and ionizing radiation. IDIBELL-Bellvitge Biomedical Research Institute

Beckman Coulter, Inc. has obtained a CLIA Certificate of Registration, along with Massachusetts State Licensure, allowing Beckman Coulter Genomics to begin accepting clinical samples for genetic sequencing – the most technically complex CLIA category – and to provide those results to physicians for their use in treating, diagnosing and preventing disease in patients.

This milestone certification paves the way for detection of BRAF exon 11 (codons 439-477) and exon 15 (codons 581-620) for mutations using PCR-based DNA Sanger sequencing, the first clinical molecular diagnostic assay the company has developed. Plans call for Beckman Coulter Genomics to develop further CLIA-certified assays using next-generation sequencing for a number of oncology and infectious disease applications.

‘This certification allows Beckman Coulter to work more closely with physicians to bring the promise of high-quality molecular diagnostics to benefit greater numbers of patients,’ said Joseph Repp, vice president and general manager of Beckman Coulter Genomics. ‘We’re actively working to bring additional assays to physicians and clinical researchers across the country, as well as help all our customers further their understanding of genetic involvement in disease states.’

In recent years it became clear that people with diabetes face an ominous prospect – a far greater risk of developing Alzheimer’s disease. Now researchers at The City College of New York (CCNY) have shed light on one reason why. Biology Professor Chris Li and her colleagues have discovered that a single gene forms a common link between the two diseases.
They found that the gene, known to be present in many Alzheimer’s disease cases, affects the insulin pathway. Disruption of this pathway is a hallmark of diabetes. The finding could point to a therapeutic target for both diseases.
‘People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy,’ said Professor Li, explaining why the link is not far-fetched.
Although the cause of Alzheimer’s is still unclear, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients’ brains.
Mutations in the human ‘amyloid precursor protein’ (APP) gene, or in genes that process APP, show up in cases of Alzheimer’s that run in families. In the study, Professor Li and her colleagues scrutinised a protein called APL-1, made by a gene in the worm Caenorhabditis elegans (C. elegans ) that happens to be a perfect stand-in for the human Alzheimer’s disease gene.
‘What we found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted,’ said Professor Li. ‘We began to examine how the worm-equivalent of APP modulated different metabolic pathways and found that the APP equivalent inhibited the insulin pathway.’
This suggested that the human version of the gene likely plays a role in both Alzheimer’s disease and diabetes.
They also found that additional mutations in the insulin pathway reversed the defects of the APP mutation. This helped explain how these genes are functionally linked.
The APL-1 is so important, they found, that ‘when you knock out the worm-equivalent of APP, the animals die,’ Li explained. ‘This tells us that the APP family of proteins is essential in worms, as they are essential in mammals,’ like us.
Professor Li and her colleagues hope that this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer’s disease and diabetes. The City College of New York.