Posts by Andreia Cunha

With a little help from your family: advances in non-invasive prenatal diagnosis

Andreia Cunha on March 4, 2013 at 6:44 pm - 0 Comments

Accurate prenatal diagnosis is important to guide pregnancy and birth management, therapeutic strategies, and future family planning, but invasive diagnostic techniques are associated with a risk of miscarriage. Advances in next-generation sequencing have allowed the development of methodologies for non-invasive prenatal diagnosis (NIPD) from cell-free fetal DNA circulating in maternal blood.

There has been much discussion recently regarding moving NIPD to the clinic, and so far this technology has been mainly applied to detection of sex-linked, single gene and chromosomal abnormality disorders. A successful example is the detection of aneuploidies, as discussed in a Review and Open debate previously published in Genome Medicine. By contrast, using NIPD to diagnose complex diseases or those caused by de …

Not a mixed bag: redefining syndromes associated with ASXL gene mutations

Andreia Cunha on February 26, 2013 at 1:59 pm - 0 Comments

Bohring-Opitz syndrome is a clinically heterogeneous developmental condition characterized by feeding difficulties, severe developmental delays, a smaller than average head circumference, and distinctive facial features and posture. It is estimated that around half of the individuals affected have de novo truncating mutations in the additional sex combs like 1 (ASXL1) gene. The ASXL gene family is composed of three evolutionarily conserved transcriptional regulators, ASXL1, ASXL2 and ASXL3 that are known to play key roles in development.

In a study recently published in Genome Medicine, and highlighted in a Nature News piece, Matthew Bainbridge and colleagues report de novo truncating mutations in the ASXL3 gene that are associated with a clinical syndrome with features partially overlapping with Bohring-Opitz. …

Return of incidental genetic findings: guidelines for clinical trials

Andreia Cunha on January 30, 2013 at 10:54 am - 0 Comments

The decrease in cost and increase in efficiency of genome-scale studies means we can enjoy fast-paced generation of genomic data. In the clinic, this growth has attracted a lot of attention and many randomized clinical trials are using genomic data. During the course of a particular trial, clinicians may stumble upon genetic findings that could have health implications, but which are of no interest to the investigation in progress – so called incidental findings. The return of these incidental findings to patients has important ethical and practical considerations, but the fast pace in the genomics field has not been matched by the publication of recommendations on how best to handle them.

The Genomics and Randomized Trials Network (GARNET) analyzes …

miRNA biomarkers in osteosarcoma: crossing a new bridge

Andreia Cunha on January 22, 2013 at 3:08 pm - 0 Comments

Osteosarcoma is the most common type of bone tumor, but the lack of good biomarkers to predict the outcome of standard treatment has so far prevented patient stratification and therapy evolution. Gene expression signatures, including microRNA (miRNA) profiles, have been suggested to have predictive value for the response of a tumor to chemotherapy, but the limited availability of frozen tissue samples has hindered development of signatures with prognostic value for recurrence and survival. Formalin-fixed paraffin-embedded tissue (FFPE) is the standard sample used by histopathological laboratories but it has proved very challenging to use this for reliable expression-profiling.

This problem has now been overcome by Dimitrios Spentzos and colleagues, whose study was recently published in Genome Medicine. The …

Cystic fibrosis modifier genes: the last refuge of the complex

Andreia Cunha on January 2, 2013 at 5:55 pm - 0 Comments

Cystic fibrosis is a rare but lethal autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is responsible for the balance of salt versus water movement in cells, and defects in CFTR lead to thickened secretions, for example in the lungs, which cause recurrent lung infections that eventually become fatal. The most common CFTR mutation is DeltaF508, in which the protein lacks a phenylalanine (F) residue at position 508. However, patients with the DeltaF508 mutation vary considerably in the severity of the clinical manifestation of cystic fibrosis, suggesting that other genetic factors contribute to disease phenotype.

These genetic factors, so called modifier genes, remain for the most part elusive, but the teams of …

Cancer mutations: separating the wheat from the chaff

Andreia Cunha on November 29, 2012 at 2:19 pm - 0 Comments

Cancer research has invested in cancer genome sequencing with the aim of identifying somatic mutations that drive tumorigenesis. Yet, the thousands of somatic mutations identified in cancer sequencing projects have little meaning without being able to distinguish the cancer-causing “drivers” from the neutral “passengers”. Identifying the mutations with a functional impact is one approach to distinguish driver from neutral mutations for further investigation.

Genes encoding critical proteins are likely to have a lower tolerance to non-synonymous single nucleotide variants (SNVs), compared with genes encoding less essential products. However, the tools available so far to assess the functional impact of mutations would not take this different baseline tolerance into account. Nuria López-Bigas and colleagues used germline variants from the 1000 …

Highlights of the October issue of Genome Medicine: A gene expression signature in glioblastoma neural stem cells, changes in the skin microbiome composition with puberty, advances in salivary biomarker technology, the future of single-cell genomics, and more

Andreia Cunha on November 12, 2012 at 11:12 am - 0 Comments

The October issue of Genome Medicine features articles covering a range of topics across our broad scope. The issue starts with Michael Wigler’s musings on the future applications of single-cell technologies for basic cell biology and biomedical research beyond cancer. Two reviews were also published in October; one by Tamim Shaikh and colleagues discussing the advantages and limitations of copy number variation analysis in clinical diagnostics as well as the impact of this on clinicians and patients. Another review, by Nicolai Bonne and David Wong, explains why saliva is a promising diagnostic sample and provides an overview of the recent technical innovation in this area, such as analyte stabilization, nucleic-acid pre-amplification …

The September issue of Genome Medicine: Annotate-it, de novo mutations in neurological and psyquiatric diseases, epigenomics of ulcerative colitis, and more

Andreia Cunha on October 5, 2012 at 5:07 pm - 0 Comments

The September issue of Genome Medicine opens with two research highlights discussing recent articles providing novel insights into the pathophysiology and treatment of chronic obstructive pulmonary disease and ulcerative colitis, inflammatory conditions with increasing incidence worldwide.

On the topic of chronic obstructive pulmonary disease, Silke Meiners and Oliver Eickelberg discuss a research article published in the August issue of Genome Medicine, emphasizing how the pioneering database-driven drug discovery approach used in this study may be useful in finding more efficient therapies for chronic lung diseases in general. In the article on ulcerative colitis, Eamonn Quigley discusses a recent epigenome-wide association study by Philip Rosenstiel and colleagues, highlighting how it provides the first …

Genome Medicine at the Next-Generation Sequencing conference

Andreia Cunha on September 26, 2012 at 11:12 am - 0 Comments

The Next-Generation Sequencing (NGS) conference organized by SMi was held in London on 17 and 18 September and Genome Medicine was there. As the Personalized Medicine Head of Unit at the European Commission, Patrick Kolar, pointed out in his opening remarks, the exponential growth in this field has been facilitated by the drop in the cost of technology, similar to the advances in the 19th century once aluminium production was made possible. We won’t be writing about aluminium, but will instead cover interesting aspects presented in this meeting for those who could not attend.

Wilhelm Ansorge discussed that we are living in the time of “Next-Generation fever”. He explained why in his overview of the latest developments in …

July highlights from Genome Medicine: medical genome sequencing, gene-environment interaction, and more

Andreia Cunha on August 6, 2012 at 1:23 am - 0 Comments

The July issue of Genome Medicine includes two articles focusing on medical research for personalized cancer therapy. Firstly, a research article by John Carpten’s group used whole genome sequencing to analyze the somatic mutations and structural aberrations present in a tumor of the ampulla of Vater resected from a patient. This is a rare form of gastrointestinal cancer and often treated as distal common bile duct or pancreatic cancer. This study suggested a distinct molecular origin for tumors of the Ampulla of Vater, and also revealed potential therapeutic approaches.

Secondly, a comprehensive review by Alfonso Valencia and Manuel Hidalgo discusses the critical bioinformatic issues that need to be overcome for the rapid and effective …