Multifactorial Inheritence

Question 1

Multifactorial Traits Definition

Answer 1

• Among genetic disorders in humans, single gene and cytogenetic abnormalities are greatly outnumbered by common disorders that appear familial but are neither determined by single genes nor abnormalities in chromosome number or structure. These disorders are known as multifactorial traits or multifactorial conditions, indicating that there are many factors involved in their causation, including both multiple genes and environmental influences.
• Multifactorially determined disorders may be congenital or they may present in postnatal life, either in childhood or in adulthood. The major burden of multifactorial disorders such as diabetes and cardiovascular disease is in adult populations. Taken as a whole, this group of disorders accounts for the majority of human morbidity and mortality.

Question 2

Principles of Multifactorial Inheritance

Answer 2

• the number of affected relatives
• the relationship of the affected individual to the consultand
• the severity of the defect
• the sex of the affected individual.

Question 3

Qualitative Traits

Answer 3

• Multifactorial traits that are either present or absent are known as qualitative, or discrete traits.
• This includes problems such as cleft lip and palate, neural tube defects such as spina bifida and anencephaly and the fetal alcohol syndrome with its obvious environmental contribution.

Question 4

Quantitative Traits

Answer 4

• These are traits that generally have a continuous distribution in the population. We define “disease” of a quantitative trait by taking the extremes and arbitrarily defining them as “abnormal” (in practice these extremes are usually defined as 2 standard deviations above or below the population mean).
• Classical examples of quantitative traits include height and intelligence.

Question 5

We share [] of our alleles with first-degree relatives, [] with second-degree relatives and [] with our third-degree relatives.

Answer 5

We share one half of our alleles with first-degree relatives, one-fourth with second-degree relatives and one-eighth with our third-degree relatives.

Question 6

There are two important lines of evidence that point to a genetic contribution to both common human diseases such as diabetes and to birth defects such as cleft lip and palate.

Answer 6

(1) There is a generalized familial aggregation for many diseases and birth defects that is proportionate to the degree of relatedness.
(2) Twin studies show that monozygotic twins are more likely to have these diseases or birth defects than are dizygotic twins.

Question 7

Familial Aggregation

Answer 7

The familial aggregation of a disease may be measured by the relative risk ratio λr, which is defined as the prevalence of a disease in a relative of an affected person divided by the prevalence of the disease in the general population. A λr of 1 means that a family member is no more likely than anyone in the general population to have the disease, which indicates no or very little genetic contribution to the disorder. By contrast, the higher the λr, the greater the influence of genetic factors.

Question 8

Monozygotic Twin Studies

Answer 8

Monozygotic twin studies provide very good evidence of the multifactorial nature of many birth defects and other diseases. Remember that monozygotic twins share 100% of their genome since they are the result of division of a single zygote, while dizygotic twins share 50% of their genome, since they are the result of separately fertilized ova. One would therefore expect single gene disorders to be 100% concordant (both twins being affected) in monozygotic (MZ) twins and 50% concordant in dizygotic (DZ) twins. One would also expect that a completely nongenetic disorder would be equal in both MZ and DZ twins. As it turns out, multifactorial traits are not 100% concordant between MZ twins, nor are they equal between MZ and DZ twins. This indicates that they are neither wholly genetic nor wholly nongenetic, but rather have both genetic and environmental components. Table 8-4, p 155 illustrates the concordance rates for 9 separate disorders among MZ and DZ twins.

Question 9

The threshold model of multifactorial disorders

Answer 9

The model that has been developed to explain observed phenomena about multifactorial conditions has been termed the threshold or risk threshold model. Remember that multiple genetic loci are involved in the continuous distribution of polygenic and multifactorial traits. In the risk threshold model there is assumed to be a continuous distribution for genetic liability for many traits such as cleft lip. At the highest end of genetic liability continuum are people who exceed a risk threshold and are therefore affected. Again, when there is sharing of risk alleles, as there is among relatives, there is an increased risk that is generally proportionate to the degree of relatedness.