Deviations from Mendelian Genetics


Resources: Presentation Chapter 15 and Protocol Chapter 15.

It may be that an allele expected to influence the phenotype does not (E.g. No clinical symptoms for a disease-causing mutation). Furthermore, it can be seen that individuals with an identical genotype show variable phenotypic expressions.

Expressivity = degree of the phenotypic expression of a given trait. 

When a trait is not manifested at all in some patients, it is said to experience ‘incomplete penetrance.’
Penetrance = proportion of patients, in which a particular genotype is actually expressed in the corresponding, expected, phenotype.
Note: Complete Penetrance is the usual Mendelian monogenetic inheritance.

Polydactyly (Dactylos = finger)

Cause: Autosomal DOMINANT Mutation
Gene: GLI3
Penetrance: 65%

Polydactyly

Familial Breast Cancer

Cause: Autosomal DOMINANT Mutation
Gene: BRCA1
Penetrance: 80%

Sex Limited and Sex-Influenced Traits

Sex limited and sex influenced traits are driven by genes located on autosomes. Their phenotype expression differs in both sexes, and those differences are caused by the presence of sex hormones in males and females.

Sex-limited traits are genetically determined in both sexes, yet they are expressed in one gender only (E.g. facial hair).

Sex-influenced traits are genetically determined in both sexes, but are expressed predominantly in one gender and less often in the other – i.e. the phenotypic expression differs according to gender (E.g. hair loss in men related to high lvls. of testosterone).

Gene-Linkage, Gene Recombination

Two genes located in close proximity on a chromosome have lower chances of being separated during crossing over. The alleles of these genes are frequently inherited together in their original arrangements (haplotypes). This is referred to as a linkage-group.

Complete linkage = The genes are so close that in most of the cases they are not separated
Incomplete linkage = The genes are close together, but they may be separated. They undergo recombination with a certain frequency.

Example:

The HLA (Human Leukocyte Antigen) system is an example of a linkage-group which includes the genes for membrane glycoproteins found on a cell surface and serving for cell recognition – antigens of the major histocompatibility complex (MHC).
These antigenes are coded for by several distinct genes located at different, but close, loci on chromosome 6. These antigens are responsible for the acceptance or rejection of a transplant.

The alleles of the HLA system also show codominance.

Inheritance of Quantitative traits

Usually, a trait(most morphological, biochemical and mental traits) is determined by more than one gene (see HLA example). These traits are called quantitative traits. The inheritance of a quantitative trait is termed polygenic, or multifactorial (Note: The environment is counted as a factor when talking about multifactorial inheritance).

A single gene may be responsible for a variety of traits.  This is called pleiotropy.

Polygenic diseases:

  • Phenylketuronia
  • Arterial Hypertension
  • Type 2 Diabetes
  • Myopia
  • Schizophrenia
  • etc.