“New sequencing technologies allow us to sequence the complete human genome in a matter of days”
genome that makes each individual genetically unique, especially involving disease-causing mutations (nucleotide changes, deletions, insertions, inversions, or translocations) and gene copy number variations (CNVs). Both mechanisms are commonly involved in the molecular pathology of congenital malformations, neurocognitive and/or mental retardation syndromes as well as several malignant disorders. Recent advances in high-throughput DNA
genotyping techniques and their improved economies allowed the rapid expansion
of the number of newly identified genetic variations and the availability of thousands of databases that contain different types of genetic or clinical data. These conditions have also favoured the launch of the international HapMap project with the aim to publish a genome variation map. In fact, the HapMap is a haplotype map of the human genome, which describes the common patterns of human DNA sequence variation. It catalogues the patterns of small-scale variations in the genome that involves mainly single nucleotide polymorphisms (SNPs). On the other hand, sequence-based
maps of large-scale structural variation across the human genome are also available. These types of variations involve genome sequences that range from a few thousand to a few million DNA bases; some are gains or losses of stretches of genome sequence and others appear as re-arrangements of stretches of sequence. These variations include differences in the number of copies individuals have of a particular gene, deletions, translocations
Figure 1: Counts of genome wide association studies that contributed to the depiction of the molecular etiologies of various Mendelian disorders in Arab consanguineous families.
and inversions; hence the name copy number variations (CNV)s. Besides their evolutionary significance,
Figure 2: Schematic representation of the percent gene-related articles of the total number of biomedical records surveyed at the Centre for Arab Genomic Studies (July 2010).
the availability of variation maps brings about immense medical applications. One way to express that is the assessment of genetic variation on drug response in patients by correlating gene expression or single- nucleotide polymorphisms with a drug’s efficacy or toxicity. Such type of studies have lead to the birth of the new field of pharmacogenomics that aims at developing rational means to optimize drug therapy, with respect to the genome background of an individual, to ensure maximum efficacy with minimal adverse effects; hence the term, Personalized Medicine. From another medical perspective, the study of human genetic variation is also important because some disease causing alleles occur at a greater frequency in people from specific geographic regions. Such differences in allele frequencies contribute to group differences in the incidence of some monogenic diseases, and they may contribute to differences in the incidence of some common diseases. For example, a long-term project to catalogue genetic disorders in Arab populations was launched in 2004 at the Centre for Arab Genomic Studies. The CTGA Database resulting from this project currently indicates the presence of 980 genetic disorders among Arab individuals. While most of these disorders are rare entities, major disorders are available at epidemic levels and cause great impact on local healthcare systems. This group encompasses all hemoglobin disorders (thalassemias, sickle cell disease, and hemoglobin variants), G6PD deficiency, Down syndrome, cancers (breast, ovarian, cervical, lung, intestinal), diabetes, Alzheimer’s disease, anencephaly, hypercholesterolemia, essential hypertension, neural tube defects, polycystic kidneys, and many others. Some other disorders do occur in Arab populations at higher incidence rates when compared to world data, these include: Tetralogy of Fallot, familial Mediterranean fever, deafness, Noonan syndrome, Meckel syndrome, and spondyloarthropathy. In the case of monogenic diseases,
the frequency of causative alleles usually correlates best with ancestry, whether familial, ethnic, or geographical. In certain cases, the distribution of diseases is best
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