Genetics, revised edition. Karen Vipond

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Genetics, revised edition - Karen Vipond


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3.6 Estimation of risk from two homozygote parents

      Offspring have a:

      • 1 in 1 chance or 100 per cent risk of being affected.

      Affected individuals who are homozygous recessive are usually the offspring of one of the above three matings.

      There are thousands of autosomal monogenic recessive conditions. Table 3.1 contains a few examples of the most common conditions.

Condition Chromosome Gene Effect
Adenosine Deaminase Deficiency20qADASevere combined immunodeficiency
Batten Disease16pCLN3Progressive disorder resulting in neuronal death within the brain
Congenital deafness11pUSH1CDeafness
Cystic Fibrosis7qCFTRDefective chloride ion transport leading to thickened mucus production
Galactosaemia9pGALTDevelopmental delay as a result of inefficient metabolism of galactose
Gaucher Disease1qGBABuild-up of fatty deposits on liver, spleen, lungs and brain; anaemia and joint problems
Hereditary Haemochromatosis6pHFEIron overload due to too much iron being absorbed from the small intestine
Maple syrup urine disease7qDLDMetabolic disorder leading to seizures, failure to thrive and developmental delay
Oculocutaneous Albinism11qTYRLack of pigment in hair, skin and eyes
PKU12qPAHIncreased levels of phenylalanine leading to brain damage
Sickle Cell Anaemia11pHBBAbnormal haemoglobin. Sickle-shaped red blood cells, which lead to the blocking of small blood vessels
Spinal Muscular Atrophy5q1120SMN1IGHMBP2VAPBProgressive loss of function of motor neurones leading to atrophy of muscles
Tay-Sachs15qHEXABuild-up of fatty deposits in the central nervous system, leading to death

      Additional risks

      Everyone carries several ‘faulty’ recessive genes that have no impact on their health. There are many different forms of faulty genes within a population but, because genes are inherited from parents and grandparents, family members will have more similarity within their genes and shared ‘faulty’ genes.

      Consanguinity

      The risk of developing an autosomal recessive genetic condition is increased in offspring of consanguineous relationships. The term consanguinity derives from the Latin prefix con-, meaning ‘together’, and the word sanguis which means ‘blood’. It describes the marital relationship between two individuals who share a common ancestor. The most common form of consanguinity is the marriage between first cousins, which is encouraged in some cultures.

      The children of unrelated parents are at low risk of inheriting two copies of the same faulty or altered allele. The risk of having a child with a birth defect is between 2 and 3 per cent, some of which will be due to a genetic condition. Children of parents who are blood relatives have an increased risk of having a genetic defect. The risk is doubled for parents who are cousins (5 to 6 per cent). The risk of inheriting the same faulty gene from both parents is increased the closer the relationship is between the parents (i.e. the more genes that they have in common) (see Table 3.2).

Relationship to each ot herBrothers/sisters Parent/childUncles/aunts Nephews/niecesGrandparentsHalf-brothersHalf-sistersFirst cousins Half-unclesHalf-auntsHalf-nephewsHalf-nieces
Relationship typeFirst-degree relativesSecond degreeThird degree
Proportion of genes that they have in commonHalf 50 per centQuarter 25 per centEighth 12.5 per cent

      The risk of having an affected child is much higher than 5 to 6 per cent in some families, because parents who are first cousins might also have grandparents who are themselves related.

ACTIVITY 3.1

      a. A child who has a recessive genetic condition has two unaffected parents. If the child’s genotype for this disorder is bb, what are the genotypes of the parents?

      b. Why do recessive conditions appear to ‘skip’ generations?

      AUTOSOMAL DOMINANT INHERITANCE

      Autosomal dominant single gene disorders occur in individuals who have a single altered copy of the disease-associated allele. An alteration in only one of the alleles within a gene is enough to cause the disorder. The mutated disease-causing allele can be inherited from either parent.

      Alleles encode for the production of a specific protein. When one allele is altered, in that the specific protein is no longer produced, the remaining functioning allele will still continue to encode for the specific protein. In autosomal dominant disorders, the amount of protein being encoded for by the functioning allele is not enough for the body to function normally. In these cases the faulty allele causes a problem for the individual as it is dominant in its effect over the functioning normal allele.

      In individuals who possess both alleles in an altered form (homozygous dominant), the disease symptoms are generally more severe. Dominant disease allele homozygotes are quite rare as many conditions appear lethal in the homozygous dominant form.

      Rules of autosomal dominant inheritance

      • Both males and females are equally affected, and can transmit to both sons and daughters.

      • Most affected individuals will have an affected parent. The disease does not ‘skip’ generations.

      • In affected families, where one parent is affected, the risk of transmitting the trait to the offspring is 50 per cent.

      • If both parents are unaffected, none of the children will be affected.

      Inheritance patterns

      Affected individuals, who possess a dominant allele, are produced via one of three different types of mating.

      1. Two homozygous dominant parents: AA x AA (both parents are affected) (see Figure 3.7).

      Key: A = dominant affected allele, a = recessive normal allele.

      The estimation of risk of an affected offspring is 100 per cent (see Figure 3.8).

      Offspring have a:

      • 1 in 1 chance or 100 per cent risk of being affected.

      2. Two heterozygous parents: Aa x Aa (both parents are affected) (see Figure 3.9).


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