Please enable JavaScript.
Coggle requires JavaScript to display documents.
L24 - Gene Interaction
Sex-linked characteristics (& basics of…
L24 - Gene Interaction
- Sex-linked characteristics (& basics of determination)
- Mosaicism
- Mitochondrial inheritance
- Penetrance & expressivity
- Gene interaction & epistasis, with emphasis on recessive epistasis (not exact CH2O)
X Inactivation - Monoallelic Expression
- Occurs early in development.
- Human females are “functionally mosaic (cells will express the paternal/maternal X-chromosome independently of one another”)
- Most of the genes on one X chromosome are
inactivated in every cell.
- Silencing of one X chromosome is random (each cell has independent choice).
- All descendants of that cell keep the same pattern.
Mosaicism
Are Post-zygotic mutations resulting in two or more genetically distinct cell lines. - one of which bears a disease causing mutation
Two Types
(B) A mutation arising later will be more localised.
(Similar to, but not the same as, somatic mutations
-
(A) A cell mutating early in development will have descendants in many tissues.
(Similar to, but not the same as, germline mutations)
-
Consequences
- Mix of cells producing normal & abnormal proteins.
- Phenotype depends on proportion of cells producing abnormal protein & distribution of those cells.
- Mosaicism typically results in milder disease - does not lead to a complete loss of the DNA content of the chromsome.
Defining Mosaicism
Mosaicism can be for chromosomal or single gene disorders.
Mosaicism may affect either somatic or germline tissues.
Somatic mosaicism can result in a range of abnormalities depending on the amount & distribution of normal cells (e.g. mosaic Down syndrome (only some cells have trisomy 21), non-inherited cancers).*
-
Somatic Mosaicism
Typically results in segmented or "patchy" manifestation, though this is depended on which cell lineage is diseased and at which stage of development this mosaicism occurs
Timing of Mutation effects Degree of disease
If before separation of germline from somatic cells;
- mutation present in both germ+som & transmitted to offspring in complete form, & expressed somatically in mosaic
form.
Somatic Mosaicism is milder than complete mutation
Somatic mosaicism documented in many X-linked disorders in both males & females.
- E.g. a case of dysfunction of hepatic urea cycle due to deficiency of ornithine transcarbamoylase (OTC) in a boy
Molecular analyses revealed that the boy had somatic mosaicism for a deletion in OTC gene => mild form of deficient OTC because mosaic
Germline Mosaicism
A mutation occurs in a germline cell & persists in all clonal descendants of that cell.
Due to mosaicism, only a proportion of gametes will carry the mutation.
High chance for mosaicism to occur during mitosis and before meiosis (~30 mitotic division before meioisis and more in males)
All or part of a parent’s germ line is affected by mutations, but their somatic cells are not.*
Lethal forms of Osteogenesis imperfecta may be due to Germline Mosaicism
-
-
-
Skewed X chromosome inactivation
Instead of X-Inactivation being random, it is more common that inactivation is skewed.
- As a consequence individuals who would typically be heterozygous carriers will actually be affected and express diseased phenotypes
-
Mitochondrial Inheritance
- Consists of a circular 16.5 kb chr.
- Multiple mtDNA Chr. per cell
- (Most cells contain at least 1000 mtDNA molecules, distributed among hundreds of individual mt)
- Current Understanding = 37 genes
- 13 encode polypeptides
- 2 rRNA = produce mitochondrial proteins
- 22 tRNAs
Mitochondrial Mutations
Exhibit a distinctive pattern of inheritance on account of three unusual features
-
3. Maternal Inheritance
- Females pass on mitochondrial DNA to children => therefore they pass on mt-diseases too
- Whilst affected males do not generally pass on to offspring
-
1. Replicative Segregation
Copy their own genome and the distribution acrossprogeny during mitosis (cytokinesis) is random. The mitochdria organelle itself segregates randomly across the progeny cells
Polygenic Interactions Continued
Multiple genes, across a number of loci, contribute to a single phenotype
- Gene products combine to produce new phenotype which aren't able to be predicted if considering a single locus in isolation
- Interaction produces novel phenotype
Encoding Enzymes
Gene products commonly will interact in biochemical pathways. For instance, each gene encodes an enzyme which regulates steps in a metabolic pathway, the products of which determine phenotype
Epistasis
Actions of genes that are encoded at one loci, impact the expression of genes at another loci
Similar/dissimilar to dominance interactions, however the key difference being that in dom. loci iof interacting genes are the same.
-
-
-
-