A practice known as genome-sequencing has opened up the potential for significant advances in genetic screening for diseases such as cancer and Alzheimer's
August 12, 2015 15:51
By
Bonnie Estridge
Recently, Angelina Jolie talked openly about the need to publicise tests for genetic mutations, otherwise known as faulty genes - in her personal case, those involving breast and ovarian cancers .
The award-winning actress recently endured a double mastectomy and had her ovaries removed after discovering that she had a deadly mutated version of the BRCA1 gene (which men also carry) and is considerably more common among Ashkenazis than the rest of the population.
Sadly, Angelina's mother, Marcheline Bertrand, died of cancer at a young age, and Angelina revealed that she wanted to reassure her six children she would not also die young and that this was why she had the surgery. Although she is not Jewish (she is of French-Canadian descent) her genetic profile puts her - like all Ashkenazi Jewish women - in a higher risk category for the deadly mutation of this gene.
It is these mutations - not the genes themselves - which cause the problem as each mutation increases significantly the likelihood that a carrier will develop breast cancer or ovarian cancer in their lifetime.
There are a number of genetic diseases of which those of Jewish heritage (at least one grandparent) are more likely to be carriers of the BRCA1 gene than the general population. Yet it is also estimated that nearly one in two Ashkenazi Jews in the US is a carrier of at least one of 38 Jewish genetic diseases, many with surprising names, such as Maple Syrup Urine Disease, Niemann-Pick Disease, Canavan Disease, Walker Warburg and Tay Sachs.
A rather more widely known disease is cystic fibrosis, which has a carrier rate of 1 in 24 in Ashkenazi Jews according to the Jewish Genetic Disease Consortium. In fact, carriers are likely to be healthy individuals who are unaffected by the disease. But if both parents are carriers of a gene mutation for the same condition then there is a 25 per cent chance with each pregnancy of having an affected child. The diseases are all serious and can be fatal or life-altering to children born with them.
According to the UK charity Breast Cancer Campaign, there are three known BRCA mutations in people of Ashkenazi Jewish descent. The frequency of the mutations in this particular case is around two per cent, which is higher than the average in the general UK population.
But now a practice known as genome-sequencing is becoming more affordable and routine, and this has opened up the potential for significant advances in genetic screening for diseases such as cancer and Alzheimer's, but also those that are lesser known.
In a unique experiment carried out in the US, an American Jewish family of Ashkenazi origin volunteered to have its genome (the map of their DNA) "sequenced" as part of a project designed to improve the accuracy of genetic testing and disease diagnosis. They appear to have stumbled upon some interesting genetic findings in the process.
The family consists of Leon, a scientist, who is 45, his mother, Klavdiya, father, Miron, and his four-year-old son Eleazar. Leon and his parents are playing a pioneering role in a groundbreaking project called Genome in a Bottle, a consortium organised by the US National Institute of Standards and Technology with Horizon Discovery, a British UK company based in Cambridge. The company is providing genetic reference material to support this project.
The genome itself carries the full set of an individual's total genetic material, which consists of over three billion "base pairs" (units).
Each genome contains all the information needed to build that organism and within the DNA is a unique chemical code that guides our growth, development, eye colour, height, health and so on.
Researchers have been able to test certain genes for years, but the ability to sequence the human genome creates an entire genetic "map" of an individual's DNA which opens up significant opportunities to identify predisposition to disease.
"Since the first whole human genome was sequenced around a decade ago the cost of the procedure has fallen significantly, from over £1.3 billion to roughly £700," says Dr Paul Morrill of Horizon Discovery. "This brings genome sequencing within reach of ordinary people and also means that within a generation it could be routinely used as a public health tool. But there are still significant discrepancies in the quality and accuracy of the data that is generated. The major undertaking of Genome in a Bottle aims to improve the reliability of 'genetic material', which is increasingly being used for diagnosing and treating diseases. This is important because of the need to ensure that these new tests are as accurate as possible. Finding alterations within a patient's genetic code can be like searching for a needle in a haystack. In the case of cancer, a single alteration within your human genome consisting of three billion base pairs can be the difference between having, and not having, an effective drug therapy. Accurate diagnostics are therefore crucial."
Leon's family was keen to get involved in this project, which is designed to provide a complete genomic map to help researchers standardise the reference material they need, and this is the first example of an inter-generational genome screening project for research. So now whole genome sequencing is going to take this to a new level simply because it is the complete code of everything in our bodies. Miron, Leon's father, has twice survived cancer and this prompted his son to learn more about his own genetic history. The screening programme revealed, for example, that both his parents were carriers of genes that predisposed them to Alzheimer's, but that Leon - who is a scientist - has avoided inheriting this gene.
"All of my grandparents lived to be over 80 and my parents have also lived long and healthy lives," he reveals. "So short of recessive variants converging in me, I did not feel that I had too much to worry about.''
However, Leon did discover from the screening that he is a recessive carrier for cystic fibrosis and also a condition called prostate adenoma, a tumour that is usually benign but can become malignant. He says: ''As more and more people seek to find a genetic road map to improve the chances of maximising their health, I hope my family's experience will provide a valuable contribution to the development of biomedical science."
