Individualized medicine enabled by genomics in Saudi Arabia

Molecular Genetics & Genomic Medicine, 2018

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Extraordinary developments in genomics research, technologies and ensuing knowledge are creating the potential of astonishing changes in both the healthcare and the life sciences sectors. For instance, next generation sequencer technology is technically progressing at a very rapid pace making it multiple folds faster than five years ago. The genomics innovations include the following: 1) Adoption of Next Generation Sequencing (NGS) ? based testing such as Whole Exome and Genomic Sequencing (WES & WGS) in clinical service as a diagnostic test including so-called direct-to-consumer genetic testing services, 2) Moving toward single cell sequencing study in heterogeneous cells and/or genetic make-ups, 3) Evolution of NGS ? based RNA sequencing field, i.e., measuring the gene expression changes along with non-coding RNA (Whole Transcriptome Sequencing), 4) Pharmacogenomics, and 5) Circulating Tumor Cells (CTCs), circulating cell-free DNA (cfDNA), and mitochondrial DNA (mtDNA) as non-invasive real-time circulating blood biomarkers surrogates for tissues. This paper looks at the impact of clinical genomics disruptive innovations on the healthcare system in order to provide better diagnosis and treatment. The genomic trends will not only transform point-of-care but also it will further facilitate progression towards personalized medicine to offer tailored and/or targeted treatment to patients, i.e., personalized therapy with the promise to improve patient?s lives. A special reference will be made to the Gulf region genome projects and personalized healthcare plans for ultimately to offer better prevention, diagnosis and treatment for its population. In particular, Qatar?s efforts in the genomic medicine area will be emphasized including the private Applied Biomedicine Initiative (ABI).

International Journal of Innovative Research in Medical Science

Next generation genomic tools including dense SNP arrays and high throughput sequencing technology have led to the exponential increase in delineating genetic defects in rare as well as common genetic disorders. Advanced genetic tools have found clinical applications in almost all areas of medicine specifically in clinical diagnostic setting. Genomic testing has entered clinical practice and physicians are using genomic information to guide treatment options. Medical schools throughout the world have integrated medical genetics and genomics courses in the curriculum to prepare medical students and future physicians to understand the role of genetic factors in human health and disease. However, in Saudi Arabia, the existing undergraduate curriculum in most of the medical schools is insufficient to prepare medical students to cope with rapidly advancing genomic science. Moreover, the majority of medical schools in Saudi Arabia have no geneticist as an academic staff, and where there a...

Human genetics, 2017

In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants. While recessive mutations dominated the landscape of solved cases (71% of mutations, and 97% of which are homozygous), a substantial minority (27%) were solved on the basis of dominant mutations. The highly consanguineous nature of the study population also facilitated homozygosity for many private...

2021

Despite recent biomedical breakthroughs and large genomic studies growing momentum, the Middle Eastern population, home to over 400 million people, is under-represented in the human genome variation databases. Here we describe insights from phase 1 of the Qatar Genome Program which whole genome sequenced 6,045 individuals from Qatar. We identified more than 88 million variants of which 24 million are novel and 23 million are singletons. Consistent with the high consanguinity and founder effects in the region, we found that several rare deleterious variants were more common in the Qatari population while others seem to provide protection against diseases and have shaped the genetic architecture of adaptive phenotypes. Insights into the genetic structure of the Qatari population revealed five non-admixed subgroups. Based on sequence data, we also reported the heritability and genetic marker associations for 45 clinical traits. These results highlight the value of our data as a resourc...

npj Genomic Medicine

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop “QChip1,” an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 108 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs. QChip1 had a concordance with whole-genome sequencing of 99.1%. Testing of QChip1 with 2707 Qatari genomes identified 32,674 risk variants, an average of 134 pathogenic alleles per Qatari genome. The most common pathogenic variants were those causing homocystinuria (1.12% risk allele frequency), and Stargardt disease (2.07%). The majority (85%) of Qatari SGD pathogenic variants were not present in Western po...

Global cardiology science & practice, 2014

Genetic disorders are not equally distributed over the geography of the Arab region. While a number of disorders have a wide geographical presence encompassing 10 or more Arab countries, almost half of these disorders occur in a single Arab country or population. Nearly, one-third of the genetic disorders in Arabs result from congenital malformations and chromosomal abnormalities, which are also responsible for a significant proportion of neonatal and perinatal deaths in Arab populations. Strikingly, about two-thirds of these diseases in Arab patients follow an autosomal recessive mode of inheritance. High fertility rates together with increased consanguineous marriages, generally noticed in Arab populations, tend to increase the rates of genetic and congenital abnormalities. Many of the nearly 500 genes studied in Arab people revealed striking spectra of heterogeneity with many novel and rare mutations causing large arrays of clinical outcomes. In this review we provided an overvie...

Personalized Medicine, 2014

Journal of Genetic Counseling, 2014

The incidence of congenital anomalies and/or genetic disorders in the Omani population has reached figures greater than double the global statistics. Preference for consanguineous unions together with the fact that termination of pregnancy in Muslim communities are largely avoided, have been highlighted as contributing factors. This overview identifies a third significant aspect contributing to the elevated rate of genetic disorders in the Omani population. Namely, a lack of services that are able to offer termination of pregnancy for severe congenital anomalies, to requesting parents. In this report we select an unusual case of a family at risk for two distinct genetic disorders-6q micro-deletion and unbalanced products of conception attributed to a balanced parental translocation involving chromosome 3 and 13, to portray and examine the current situation faced by Omani couples interested in prenatal diagnosis for termination of pregnancy. Additional challenges and pitfalls to developing a prenatal diagnostic service as part of the genetic service in Oman are discussed.

Genomics and Health in the Developing World, 2012

Preimplantation genetic diagnosis (PGD) testing is the practice of obtaining a cellular biopsy sample from a developing human oocyte or embryo, acquired via a cycle of in vitro fertilization (IVF); evaluating the genetic composition of this sample; and using this information to determine which embryos will be optimal for subsequent uterine transfer. PGD has become an increasingly useful adjunct to IVF procedures. The ability to provide couples who are known carriers of genetic abnormalities the opportunity to deliver healthy babies has opened a new frontier in reproductive medicine. The purpose of the PGD is enables us to choose which embryos will be implanted into the mother. In the present study 137 families who had undergone IVF at Habib Medical Centre, were enrolled for the PGD analysis. The couple visited the clinic for the sex selection, recurrent fetal loss and with the recurrent IVF failure. 802 embryos were tested by the biopsy method and 512 are found to be normal and 290 were abnormal embryos. In this study only 24% of the embryos were transferred and the remaining was not transferred because of the abnormalities or undesired sex of the embryos. The structural and numerical abnormalities were found to be 16.8%.