Kuwaiti molecular diagnostics firm Genatak has begun offering a targeted hereditary breast cancer panel and exome sequencing services for patients with cancer, undiagnosed genetic disorders, and individuals looking to understand disease risk.
Fahd Al-Mulla, a molecular pathologist who launched Genatak about a year ago, told Clinical Sequencing News that there is a particular need for these services in the Middle East because there is a high rate of consanguineous marriages resulting in many genetic disorders. Additionally, there is a lack of knowledge about Arabic genomes and the frequency of disease-related mutations in the population.
Genatak does its sequencing within a network of laboratories that includes the UK's Oxford Gene Technology; Malaysia-based Sengenics; and Gendia, a network of genetic testing laboratories based in Belgium. Genatak is also in the midst of applying for ISO and CAP accreditation.
Additionally, the firm offers Sequenom's MaterniT21 Plus test through its partnership with Sengenics and Ariosa's Harmony test through Gendia to screen for fetal aneuploidies. And it offers a 12-gene cardiovascular test, dubbed CardioSure, also through Sengenics. Genatak is also looking to soon offer pre-implantation genetic diagnostics.
Through its partnerships, Genatak has access to 11 next-gen sequencing machines, including six Illumina HiSeq 2000 systems, two Illumina MiSeq instruments, and three of Life Technologies Ion Torrent PGMs.
Thus far, Al-Mulla said that Genatak has sequenced between 60 and 70 exomes, about 80 percent of which are individuals with a family history of cancer. Another 20 percent have been individuals looking to improve their overall health by understanding their risks for cardiovascular and other diseases. Only two families with rare genetic disorders have utilized the service, but Al-Mulla said this is an area in which he is looking to expand.
The service costs $1,500 per individual and has a turnaround time of eight weeks. Causative mutations are confirmed with Sanger sequencing, and Genatak has developed its own bioinformatics pipeline with OGT and Sengenics.
Because the firm sees so many patients concerned with cancer risk, Al-Mulla said that it also offers a 27-gene hereditary breast cancer panel for around $980. It sequences the exons of those genes, which include the BRCA1 and BCRA2 genes. However, Al-Mulla said that mutations to these genes are not common in the Arab population, even when there is a family history of breast cancer.
As such, many women that receive BRCA testing due to a family history are falsely reassured. The BRCA1 and BRCA2 mutations are not common in Kuwait because of the high rate of consanguineous marriages, Al-Mulla said, which has had a "dampening effect" on the mutations because homozygous mutations to those genes are lethal.
Aside from next-gen sequencing, Genatak also has Sanger sequencing capabilities and uses fluorescence in situ hybridization to analyze copy number variation for things like HER2 amplifications in breast cancer patients to help guide treatment.
Al-Mulla said that one of the main challenges has been patient and physician education. "The concept of God is very important in this country," he said. "So a lot of people say that whatever God brings, you have to accept it." Many equate genetic testing with playing God, Al-Mulla said. In addition, there is a fear that people's genomic sequence will be used against them, he added.
Another challenge in using sequencing to diagnose disease in Arabic populations is the fact that the major genome sequencing initiatives have not involved Arabic genomes, and Al-Mulla said that he is finding that there are major differences in polymorphisms and background mutation rates between what has been reported in the literature and his findings in sequencing Arab genomes.
"Our mutation background is not similar to what the West has experienced," he said. "So I don't know if I find a mutation if it's a [true] mutation of a polymorphism."
Al-Mulla is now involved in the Genome Arabia project, which received around $1.1 million in funding from the Qatar National Research Fund to sequence genomes from Kuwait, the United Arab Emirates, Qatar, Bahrain, Saudi Arabia, Tunisia, and Lebanon.
He said the group is sequencing around 120 whole genomes and 220 whole exomes, and will publish the first results next year.
Al-Mulla is also implementing these "normal" genomes in his exome pipeline to help determine whether specific variants are pathogenic or polymorphisms.
Even though Genatak's primary customers have been patients wanting to know their risk for cancer, Al-Mulla said he sees the biggest opportunity in diagnosing unknown, genetic disease.
Around half of all marriages in Kuwait are consanguineous, he said, so the rate of autosomal recessive genetic diseases is very high, and currently genetic testing is done "one gene at a time.".
At Genatak, Al-Mulla said he first offers exome sequencing of just the affected child. If that does not lead to a diagnosis, he will then also sequence both parents. The firm has so far sequenced affected patients from two families. In both cases, the causative mutation was identified, Al-Mulla said.
One case was an X-linked disorder, he said. In the other case, a couple had a child that had passed away at the age of one year and two other children that had died in utero. They wanted to find out the cause of their babies' deaths, so Al-Mulla's team sequenced DNA from a skin biopsy taken from the baby. He identified a putative causative variant and found that both parents were carriers. The gene is associated with calcium channel problems, including calcium deposition in arteries, which he said matched the clinical features of the three children that had passed away.
Genatak works closely with Makia Marafie, a clinical geneticist at the Kuwait Medical Genetics Center. Some patients are referred to Genatak by the center, while others seek the firm out independently. Al-Mulla offers patients counseling, and patients are offered additional counseling from the genetics center.
Another challenge in implementing diagnostic exome sequencing has been dealing with variants of unknown significance. While this is a challenge for all groups offering clinical sequencing, the problem is compounded in the Middle East, said Al-Mulla because of the lack of a population-specific reference genome. Al-Mulla said that he has started building up a database of Arab genomes to which he can compare results.
When analyzing results, if a variant is identified as a pathogenic mutation in the literature, he said the variant is usually pathogenic in his specific patient as well, so he does not need to do further analysis. But, if a putative mutation is listed as a polymorphism in the literature, "that's a problem because it might be causative in our population," he said. In these cases, he then looks for the variant in the collection of Arab genomes he has generated.
When doing diagnostic sequencing, he said he includes the variants of unknown significance in the report, specifying that they are variants of unknown significance. "The report is quite extensive," he said.
Aside from expanding services in the rare inherited disease field, Al-Mulla said Genatak will also move into pre-implantation genetic testing. For this, he said he would combine exome sequencing of the parents to identify carrier status of disease related genes. Then Sanger sequencing would be used to screen for those specific mutations in the blastomere to select only the healthy cells.