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What are genetic disorders?A genetic disorder is a disease caused in whole or in part by a "variation" (an unusual form) or "mutation" (alteration) of a gene. Genetic disorders can be passed on to family members who inherit the genetic abnormality. A small number of rare disorders are caused by a mistake in a single gene. But most disorders involving genetic factors - such as heart disease and most cancers - arise from a complex interplay of multiple genetic changes and environmental influences. Geneticists group genetic disorders into three categories:
 Geographical distributions of genetic disorders in the Arab World as for CTGA (October, 2006). How do I find more information about a specific disorder or learn whether a particular disease has a genetic component?Many human diseases have a genetic component, whether inherited or resulting from the body's response to environmental stresses like viruses or toxins. Researchers are constantly learning more about the role genes play in disease, and our knowledge is growing every day. The following online resources provide discussions of what researchers do know about the genetic component of specific diseases:
What is genetic testing?Genetic tests look for abnormalities in a person's genes, or the presence/absence of key proteins whose production is directed by specific genes. Abnormalities in either could indicate an inherited disposition to a disorder. Genetic testing includes gene tests (DNA testing) and biochemical tests (protein testing). In gene tests, DNA in cells taken from a person's blood, body fluids or tissues is examined for an abnormality that flags a disease or disorder. The abnormality can be relatively large - a piece of a chromosome, or even an entire chromosome, missing or added. Sometimes the change is very small - as little as one extra, missing or altered chemical base within the DNA strand. Genes can be amplified (too many copies), over-expressed (too active), inactivated, or lost altogether. Sometimes pieces of chromosomes become switched, transposed or discovered in an incorrect location. Gene tests use a variety of techniques to examine a person's DNA. Some tests involve using probes - short strings of DNA - with base sequences complementary to those of the mutated gene. These probes will seek their complements within an individual's genome. If the mutated sequence is present in the patient's genome, the probe will find it and bind to it, flagging the mutation. Another type of gene tests involves comparing the sequence of DNA bases in a patient's gene to a normal version of the gene. Finally, Biochemical tests look for the presence or absence of key proteins which signal abnormal or malfunctioning genes. What information can genetic testing provide?Genetic testing can be predictive, discovering whether an individual has an inherited disposition to a certain disease, before symptoms appear. Genetic tests can also confirm a diagnosis if symptoms are present. Tests can determine whether a person is a carrier for the disease. Carriers won't get the disease, but can pass on the faulty gene to their children. Prenatal testing can help expectant parents know whether their unborn child will have a genetic disease or disorder. Newborn screening tests infants for abnormal or missing gene products. Individuals in families at high risk for a disease live with troubling uncertainties about their own future as well as their children. A negative test - especially one that is strongly predictive - can provide an enormous sense of relief. A positive test can also produce benefits. In the best circumstances, a positive test enables the person to take steps to reduce risk. These steps could include regular screening for the disease or lifestyle changes, such as a change in diet or regular exercise. A positive test can relieve uncertainty, and can enable people to make informed decisions about their future. Reasons for Genetic Testing Predictive testing identifies people who are at risk of getting a disease before any symptoms appear. Predictive tests include those that screen for some inherited predispositions to certain forms of cancer, such as colon and breast cancer. Being predisposed does not mean that the individual will get the disease. It means the person has a certain risk of developing the disease. Carrier testing can tell individuals if they are carriers of an inherited disorder that they may pass on to their children. A person who has only one abnormal copy of a gene for a recessive condition is known as a carrier. Carriers won't get the disease, but can pass on the defective gene to their children. Cystic fibrosis and Tay-Sachs disease are examples of disorders for which parents can be carriers. Prenatal testing is available to people at risk for having children with a chromosomal abnormality or an inherited genetic condition. Two procedures are commonly used in prenatal testing. Amniocentesis involves analyzing a sample of amniotic fluid from the womb. CVS (chorionic villus sampling) involves taking a tiny tissue sample from outside the sac where the fetus develops. Prenatal testing is often used to look for disorders such as Down syndrome, spina bifida, cystic fibrosis, and Tay-Sachs disease. Newborn screening, the most widespread type of genetic testing, tests infant blood samples for abnormal or missing gene products. For example, infants are commonly screened for Phenylketonuria (PKU), an enzyme deficiency that can lead to severe mental retardation if untreated. How should I decide whether to be tested?The decision to undergo testing is a very personal one. For many people, a pivotal consideration is whether there are preventive measures that can be taken if the test result is positive. For example, those who test positive for inherited forms of breast or colon cancer can benefit from preventive measures, screening for early detection, and early treatment. In contrast, there are no preventive measures or cures for Huntington's disease. But a positive test for Huntington's disease might help an individual make lifestyle decisions, such as career choice, family planning or insurance coverage. Because the decision about whether to be tested for a genetic disease is complex, most people seek guidance from a genetic counselor trained to help individuals and families weigh the scientific, emotional and ethical considerations that impact on this decision. What are genetic counselors and what do they do?Genetics counselors are health care professionals with specialized graduate degrees and experience in medical genetics and counseling. Genetic counselors work as members of health care teams providing information and support to individuals or families who have genetic disorders or may be at risk for inherited conditions. Genetic counselors will help:
How do I find a genetic counselor?Your doctor may refer you to a genetic counselor. Universities and medical centers also often have affiliated genetic counselors, or can provide referrals to a counselor or genetics clinic. As we've learned more about genetics, counselors have grown more specialized. For example, counselors may specialize in a particular disease (such as Parkinson's disease), an age group (such as adolescents) or a type of counseling (such as prenatal). How do I decide whether I need to see a geneticist or other specialist?A genetics counselor may refer you to a geneticist - a medical doctor or medical researcher - who specializes in your disease or disorder. A medical geneticist has completed a fellowship or has other advanced training in medical genetics. While a genetic counselor may help you with testing decisions and support issues, a medical geneticist will make the actual diagnosis of a disease or condition. Many genetic diseases are so rare that only a geneticist can provide the most complete and current information about your condition. Along with a medical geneticist, you may also be referred to a physician who is a specialist in the type of disorder you have. For example, if a genetic test is positive for colon cancer, you might be referred to an oncologist. For a diagnosis of Huntington's disease, you may be referred to a neurologist. What do genetics researchers study and how can they help people with genetic disorders?Since the beginning of human civilization, genetic applications, in the form of selective breeding, became the foundation of agricultural process and contributed to the rise and fall of civilizations over thousands of years. More than 50 years ago, a revolution of biological thought has started when Watson and Crick elucidated the molecular structure of DNA. Some of the greatest mysteries of life could suddenly be explained by the beauty and simplicity of a chemical that shrouds, replicates, and shuffles the code of life. Subsequently, DNA became the focus of laboratories around the world. Biologists devised methods to purify, mutate, cut, and paste DNA in the test tube. They laid out the principles of gene structure and function at the molecular level. Scientists discovered the genes that control hereditary diseases and made available a variety of techniques for prenatal diagnosis. Biotechnologists have genetically modified bacteria, plants, and animals to express proteins of agricultural and medical importance. Investigators now offer DNA forensic tests that help convict criminals, exonerate the innocent, and establish paternity. Molecular geneticists are cloning mammals from adult somatic cells and are rapidly dissecting the molecular genetic mechanisms that control cell growth, aging, death, and cancer. The science of genetics has come to occupy a pivotal position in the entire theme of life and, like no other scientific discipline, has become central to numerous aspects of human existence. The limits of interdisciplinary exchanges among genetics and other sciences are growing at a rapid pace. Important contributions of molecular biology and genetics are currently materializing in the fields of medicine, pharmacology, forensic sciences, ecology, agriculture, history, psychology, textile industry, food industry, computer sciences, and computer engineering. This convergent nature of molecular genetics makes it a central innovative area with a great potential to be "the science of the 21st century". Now that a draft of the human genome map is complete, research is focusing on the function of each gene and the role that faulty genes play in disease. This will lead to improved diagnosis of diseases and a new approach to disease therapy. Researchers will create new classes of drugs based on gene sequencing and structure. These drugs, because they are targeted to specific sites in the body, will have fewer of the side effects common in many of today's medicines. Other medications will be customized for an individual's genetic profile. The potential for using genes themselves to treat disease - known as gene therapy - is the most exciting application of DNA science. This rapidly developing field has great potential for treating or even curing inherited and acquired diseases. Gene therapy will use normal genes to replace or supplement a defective gene, or to bolster immunity to disease. Currently, gene therapy research is primarily concerned with establishing the safety of this approach, rather than the effectiveness of the treatment. While there are hundreds of clinical trials and studies in progress, so far no cures have resulted. What is bioinformatics?The Human Genome Project, the first "big science" project in biology, decoded the entire human genome ahead of schedule in July 2002. Genomes of many organisms were sequenced and thousands of other organisms are under current investigation. Converting this complex data into useful information requires bioinformatics, a specialty that weds biology with mathematics, information technology, and computer science. The ultimate goal of the field is to enable the discovery of new medical insights as well as to create a global perspective from which unifying principles in biology can be discerned. Bioinformatics is a fundamentally collaborative discipline owing its very existence to the accessibility and usability of rich and extensive data sets for analysis, integration, and manipulation. It is out of this concept that the Centre for Arab Genomic Studies initiated the ambitious project to establish a comprehensive Catalogue for Transmission Genetics in Arabs (CTGA) with the aim to enlighten the scientific community and the public on the occurrence of inherited disorders in Arabs and to suggest future investigation strategies. The available resources, capable people, and the will to attain this objective have led to the realization of a successful model of the CTGA database in the UAE, now available at the public domain of the Internet. What are DNA microarrays?Most of the 30,000 human genes that make our genome have been identified. Microarrays of many human genes have been prepared and used to characterize their expression in different tissues and organs, and in cancer cells compared to their normal cell counterparts. DNA "chips" capable of monitoring the expression levels of the entire human genome are now available and are evolving rapidly, with improvements in miniaturization, reproducibility, and the development of alternative approaches to microarray synthesis. The powerful technologies of microarrays will facilitate the rapid acquisition of data that provide insight into the molecular pathologies of diseases. By ferreting out differences between hereditary forms of diseases, genetic testing is nowadays widely available and less expensive. What is a consanguineous marriage?Literally, the term consanguineous marriage is defined as marriage between blood relatives. Besides, geneticists usually classify unions between biologically related persons such as second cousins or closer as consanguineous. The genetic risk for less closely related couples differs only marginally from that in non-consanguineous unions. In many parts of the world, consanguinity is highly prevalent. In 1994, the combined population of countries where 10% of marriages are consanguineous was 732 million, excluding the populations of China and Indonesia. Furthermore, 1,468 million live in Latin America, parts of Central Africa, Northern India, Japan, and Spain where consanguinity rates vary from 1% to 10%. Throughout the Arab World, consanguineous marriage is traditionally common. Overall, around 40-50% of marriages in the Arab World are consanguineous. The specific types of consanguineous marriage vary between and within countries. First cousin marriages are the most common consanguineous bonds in the Arab World. Estimates indicate that the percentage of first cousin marriages is approximately 11.4% in Egypt, 21% in Bahrain, 29% in Iraq, 30% in Kuwait, 31% in Saudi Arabia, and 32% in Jordan.  Consanguinity rates in the Arab World. Why do some population groups maintain the practice of consanguineous marriage?Besides religion, cultural and historical factors are also important in maintaining this practice. Arabs probably practiced consanguinity since ancient times before the introduction of Islam in the 7th century. Unlike what is widely thought, Islam does not advocate or encourage consanguineous marriages. The holy sermons of the Prophet Mohammad Hadith state that “close marriages will often produce weak children.” On the other hand, marriage outside the social unit results in the propagation of influence in a bigger population. In the Arab World, the custom of consanguineous marriage results from cultural and historical, rather than religious reasons. Mistakenly, the preference for consanguineous marriage is thought to be restricted to Islamic Arab communities. In some Christian communities (e.g., Lebanon) consanguinity is also common. The Arabian culture and history as well as the geographical concentration of many population groups in small and isolated areas promoted the tradition of consanguineous marriages. Many families consider the choice of consanguineous marriage between close relatives as a way to maintain the unity of family assets. Marriage with a relative is also preferred because of the comparative ease with which premarital negotiations can be conducted and the greater stability of consanguineous union due to the advanced relationship between the female partner and her in-laws. Studies indicate that several factors influence consanguinity rates in Arabs. These factors include urban-rural residence ratios of families, education levels, and time trend. Studies in Jordan, Egypt, Lebanon, Oman, and Tunisia demonstrated a higher tendency of unions among rural than urban inhabitants. In some Arab countries, it is evident that the higher the level of education of the female partner, the lower the consanguinity rate. On the contrary, in some societies, highly educated men are more likely to be married to cousins. A plausible explanation is that since a son with higher education becomes a more valuable asset, he is pressured to remain within the family. While a declining trend of consanguineous marriages has been documented in Bahrain, Lebanon, Kuwait, and Syria, a stable trend has been reported in Jordan and Oman. Surprisingly, consanguineous marriages in Algeria and Yemen are increasing in the present generations compared to previous generations. The reason for the rising trend in consanguinity can be attributed to the increase in the availability of cousins due to high fertility. In the United Arab Emirates, consanguinity rates vary according to race, tribe, economic class, isolation of the society, and secular exposure. Despite the improvements in education, general economic conditions and health status of the population, consanguinity rate in the UAE has increased from 39% to 50.5% in one generation. Moreover, the comparison of the two generations in terms of cousin marriage preferences suggests the continuation of the same patterns in the two generations. The most common has been and still is first cousin marriages (26.2%). Indeed, parents who were consanguineous were significantly more likely to give their children away to consanguineous spouses. Interestingly, consanguinity is more common among women with educated husbands (secondary or university/high) than among women with less educated husbands. Consanguinity rates are not identical throughout the main cities of the UAE. The level of consanguinity is higher in Al-Ain (54.2%) than in Dubai (39.9%). In both cities, first cousin marriage is the commonest type (28.2% in Al-Ain versus 20.7% in Dubai). In Abu Dhabi, the consanguinity rate stands at about 32%. In addition, the increase in consanguinity rate is higher in Dubai (10.42%) than in Al-Ain (7.49%). Does consanguinity have an effect on reproductive health?While the concept of inheritance is not clear in the minds of lay people, consanguinity is linked to high incidences of congenital malformations, mental retardation, and disability. Studies indicate that in populations where the practice of inbred marriages is high, the frequency of homozygosity for autosomal conditions and the incidence of congenital anomalies, abortions, stillbirths, and early childhood deaths are expected to rise. The reason behind this observation is that the more closely two people are related, the more genes they share. A marriage between first cousins increases the risk of having a child with a severe congenital or genetic disorder by 2.5 times since parents share one-eighth of their genes. An average of 30% first cousin marriage in a population would increase the birth prevalence of many conditions by 5-15 times and their collective frequency by 5.5 times. Frequent consanguineous marriage increases the incidence of autosomal recessive disorders by 5-10 times at the population level. When first cousin marriage is considered, the risk of recessively inherited disorders is multiplied by 15-30 times; hence, doubling the total frequency of congenital and genetic disorders. The genetic disadvantages associated with consanguineous marriage are often overestimated. While the incidence of recessively inherited disorders increases because of the trend of consanguineous marriages, no effects occur in autosomal dominant or X-linked conditions. Autosomal dominant conditions result from just one copy of a deleterious mutation. Thus, having two parents with the same autosomal dominant mutation does not make an individual more susceptible than someone with only one affected parent. Similarly, just one copy of a deleterious X-linked recessive mutation will result in disease in males. Hence, having related parents does not increase the risk of a male with X-linked recessive disease. Because of the widespread practice of consanguineous marriages in the UAE, many research groups aimed their studies at understanding the relationship between consanguinity and health quality in the population. Scientific results confirmed the associations of many abnormalities with the practice of consanguineous marriages. These include: increased frequencies of recessive disorders, learning disorders in schoolchildren, psychiatric morbidity, central nervous system anomalies, reproductive wastage, neonatal audit, and cancer. |
