Prevention of autosomal recessive disorders

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Prevention of autosomal recessive disorders is focused on making it less likely that two carriers for the same hereditary disease will have children together.

Contents

Background

Autosomal recessive pattern, showing how two unaffected carriers can have a child with the disease. Autorecessive.svg
Autosomal recessive pattern, showing how two unaffected carriers can have a child with the disease.

Some genetic disorders are caused by having two "bad" copies of a recessive allele. When the gene is located on an autosome (as opposed to a sex chromosome), it is possible for both men and women to be carriers. A child of two carriers has a 1/4 chance of being affected by the disorder.

Due to carriers being unaffected (or barely affected), the bad recessive alleles can persist in the gene pool for quite a while, even if the disorder is 100% lethal.[ medical citation needed ]

Outbreeding

Most modern societies have laws regarding incest, [1] with avoiding the genetic disorders caused by inbreeding as one of the major motivations. [2]

Both social acceptance and legality of first-cousin marriage is mixed. Some jurisdictions narrowly tailor their laws to preventing inbreeding: in Maine, [3] first cousins can marry with proof of genetic counseling, while in Arizona [4] and several other states, first cousins can marry if they are old or infertile. [5]

Carrier testing

Carrier testing can help guide the decisions of couples who are at high risk, e.g.:

Couples who learn that they are both carriers may decide to part ways, adopt, or use preimplantation genetic diagnosis to select unaffected embryos.[ citation needed ]

Relation to eugenics

When a population is in Hardy-Weinberg equilibrium, the proportions of each genotype are directly determined by allele frequency as shown in this chart. Mate choice is one of the ways to move a population out of equilibrium, allowing genotype frequency to change even if the underlying allele frequencies remain constant. Hardy-Weinberg.svg
When a population is in Hardy–Weinberg equilibrium, the proportions of each genotype are directly determined by allele frequency as shown in this chart. Mate choice is one of the ways to move a population out of equilibrium, allowing genotype frequency to change even if the underlying allele frequencies remain constant.

These practices are not designed to change allele frequencies and therefore have little impact on future generations beyond the first. As a result, these practices are generally not considered to be a form of eugenics, despite overlapping goals. [9]

See also

Related Research Articles

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<span class="mw-page-title-main">Inbreeding</span> Reproduction by closely related organisms

Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically. By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and other consequences that may arise from expression of deleterious recessive traits resulting from incestuous sexual relationships and consanguinity. Animals avoid inbreeding only rarely.

<span class="mw-page-title-main">Thalassemia</span> Family of inherited blood disorders

Thalassemias are inherited blood disorders that result in abnormal hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe. Often there is mild to severe anemia as thalassemia can affect the production of red blood cells and also affect how long the red blood cells live. Symptoms of anemia include feeling tired and having pale skin. Other symptoms of thalassemia include bone problems, an enlarged spleen, yellowish skin, pulmonary hypertension, and dark urine. Slow growth may occur in children. Symptoms and presentations of thalassemia can change over time. Older terms included Cooley's anemia and Mediterranean anemia for beta-thalassemia. These have been superseded by the terms Transfusion-Dependent Thalassemia (TDT) and non-Transfusion-Dependent Thalassemia (NTDT). Patients with TDT require regular transfusions, typically every two to five weeks. TDTs include Beta-thalassemia major, nondeletional HbH disease, survived Hb Bart's disease, and severe HbE/beta-thalassemia.

<span class="mw-page-title-main">Consanguinity</span> Property of being from the same kinship as another person

Consanguinity is the characteristic of having a kinship with a relative who is descended from a common ancestor.

<span class="mw-page-title-main">Dor Yeshorim</span> Jewish genetic screening organization

Dor Yeshorim also called Committee for Prevention of Jewish Genetic Diseases, is a nonprofit organization that offers genetic screening to members of the Jewish community worldwide. Its objective is to minimize, and eventually eliminate, the incidence of genetic disorders common to Jewish people, such as Tay–Sachs disease. Dor Yeshorim is based in Brooklyn, New York, but has offices in Israel and various other countries.

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<span class="mw-page-title-main">Sex linkage</span> Sex-specific patterns of inheritance

Sex linked describes the sex-specific reading patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, X-linked dominant and Y-linked. The inheritance and presentation of all three differ depending on the sex of both the parent and the child. This makes them characteristically different from autosomal dominance and recessiveness.

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Hemoglobin A2 (HbA2) is a normal variant of hemoglobin A that consists of two alpha and two delta chains (α2δ2) and is found at low levels in normal human blood. Hemoglobin A2 may be increased in beta thalassemia or in people who are heterozygous for the beta thalassemia gene.

<span class="mw-page-title-main">Alpha-thalassemia</span> Thalassemia involving the genes HBA1and HBA2 hemoglobin genes

Alpha-thalassemia is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present.

<span class="mw-page-title-main">Beta thalassemia</span> Blood disorder

Beta thalassemias are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.

<span class="mw-page-title-main">X-linked dominant inheritance</span> Mode of inheritance

X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type. In medicine, X-linked dominant inheritance indicates that a gene responsible for a genetic disorder is located on the X chromosome, and only one copy of the allele is sufficient to cause the disorder when inherited from a parent who has the disorder. In this case, someone who expresses an X-linked dominant allele will exhibit the disorder and be considered affected. The pattern of inheritance is sometimes called criss-cross inheritance.

In medical genetics, compound heterozygosity is the condition of having two or more heterogeneous recessive alleles at a particular locus that can cause genetic disease in a heterozygous state; that is, an organism is a compound heterozygote when it has two recessive alleles for the same gene, but with those two alleles being different from each other. Compound heterozygosity reflects the diversity of the mutation base for many autosomal recessive genetic disorders; mutations in most disease-causing genes have arisen many times. This means that many cases of disease arise in individuals who have two unrelated alleles, who technically are heterozygotes, but both the alleles are defective.

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The medical genetics of Jews have been studied to identify and prevent some rare genetic diseases that, while still rare, are more common than average among people of Jewish descent. There are several autosomal recessive genetic disorders that are more common than average in ethnically Jewish populations, particularly Ashkenazi Jews, because of relatively recent population bottlenecks and because of consanguineous marriage. These two phenomena reduce genetic diversity and raise the chance that two parents will carry a mutation in the same gene and pass on both mutations to a child.

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For preventing Tay–Sachs disease, three main approaches have been used to prevent or reduce the incidence of Tay–Sachs disease in those who are at high risk:

Genetic studies on Arabs refers to the analyses of the genetics of ethnic Arab people in the Middle East and North Africa and parts of Sub-Sahara Africa where Black Arabs claim descent. Arabs are genetically diverse as a result of their intermarriage and mixing with indigenous people of the pre-Islamic Middle East and North Africa following the Arab and Islamic expansion. Genetic ancestry components related to the Arabian Peninsula display an increasing frequency pattern from west to east over North Africa. A similar frequency pattern exist across northeastern Africa with decreasing genetic affinities to groups of the Arabian Peninsula along the Nile river valley across Sudan and the more they go south. This genetic cline of admixture is dated to the time of Arab expansion and immigration to North Africa (Maghreb) and northeast Africa.

Carrier testing is a type of genetic testing that is used to determine if a person is a carrier for specific autosomal recessive diseases. This kind of testing is used most often by couples who are considering becoming pregnant to determine the risks of their child inheriting one of these genetic disorders.

References

  1. Bittles, Alan Holland (2012). Consanguinity in Context. Cambridge University Press. pp. 178–187. ISBN   978-0521781862 . Retrieved 27 August 2013.
  2. Wolf, Arthur P.; Durham, William H. (2004). Inbreeding, Incest, and the Incest Taboo: The State of Knowledge at the Turn of the Century. Stanford University Press. p. 3. ISBN   978-0-8047-5141-4.
  3. "Title 19-A, §701: Prohibited marriages; exceptions".
  4. https://codes.findlaw.com/az/title-25-marital-and-domestic-relations/az-rev-st-sect-25-101/
  5. Frommer, Rachel (2021). "The Unconstitutionality of State Bans on Marriage Between First Cousins". Cardozo Law Review de Novo.
  6. Cowan: "The last of my substantive chapters concentrates on the only two mandated premarital genetic screening programs in the world: both of them on the island of Cyprus, both of them focused on the recessive gene that, when it is doubled, causes b-thalassemia."
  7. Waheed, Fazeela; Fisher, Colleen; Awofeso, AwoNiyi; Stanley, David (July 2016). "Carrier screening for beta-thalassemia in the Maldives: perceptions of parents of affected children who did not take part in screening and its consequences". Journal of Community Genetics. 7 (3): 243–253. doi:10.1007/s12687-016-0273-5. PMC   4960032 . PMID   27393346.
  8. Aneke, JohnC; Okocha, ChideE (2016). "Sickle cell disease genetic counseling and testing: A review". Archives of Medicine and Health Sciences. 4 (1): 50. doi: 10.4103/2321-4848.183342 .
  9. Cowan, Ruth Schwartz (15 February 2009). "Moving up the slippery slope: Mandated genetic screening on Cyprus". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 151C (1): 95–103. doi:10.1002/ajmg.c.30202. PMID   19170092.