Genet 302 lec 18
What is somatic mosaicism?
The presence of two or more genetically different cell populations in one individual due to a post-zygotic mutation.
How does somatic mosaicism differ from inherited mutation?
Inherited mutations are present in all cells; somatic mosaic mutations occur after fertilization and affect only a subset of cells.
What is germline mosaicism?
A mutation present in some germ cells that can be passed to offspring but may not be present in all somatic cells.
How can somatic mosaicism arise during development?
Through a mutation during embryogenesis or embryo fusion.
What is embryo fusion in mosaicism?
Fusion of two early embryos leading to genetically distinct cell populations in one individual.
How is somatic mosaicism different from somatic polyploidy?
Somatic mosaicism is due to a rare mutation; somatic polyploidy is due to normal cell maturation.
How is somatic mosaicism different from a mosaic phenotype?
Somatic mosaicism involves different genotypes; mosaic phenotype involves different gene expression without different genotypes.
Why are Oreo/tuxedo cats not examples of somatic mosaicism?
Their coat pattern is due to gene expression differences, not mutation.
How does somatic mosaicism affect severity of genetic conditions?
It often reduces severity because not all cells carry the mutation.
Why can parental somatic mosaicism affect recurrence risk?
A parent may carry the mutation in some germ cells and pass it to multiple children.
In the first case study, which gene deletion caused Smith-Magenis syndrome?
Deletion of the RAI1 gene at 17p11.2.
What is the inheritance pattern of Smith-Magenis syndrome?
Autosomal dominant.
Why did the mother initially appear unaffected?
She was mosaic and the mutation was not detectable by aCGH in blood.
Why did aCGH show the mother as wild-type?
Because mosaic levels were too low to detect by aCGH.
How did PCR-AGE detect mosaicism in the mother?
A faint mutant band indicated the deletion was present in some cells.
What does a faint band on PCR-AGE suggest?
Mosaicism with a lower proportion of mutant cells.
How common was parental somatic mosaicism in the screened families?
4 out of 100 families.
Why can a mutation appear germline by aCGH but actually be mosaic?
Low-level mosaicism may not be detected by aCGH resolution limits.
What is the recurrence risk for future children if a parent is mosaic?
Higher than expected for a true de novo mutation because some germ cells carry the mutation.
If a parent is mosaic, what outcomes are possible for the next child?
Wild-type or affected; mosaicism itself is not inherited as mosaicism.
Why can new mutations still occur in children of mosaic parents?
Independent de novo mutations can arise during embryogenesis.
What is preimplantation genetic diagnosis (PGD)?
Genetic testing of embryos before implantation during IVF.
When is PGD useful?
When one or both parents are carriers of a genetic condition.
What is Step 1 of PGD?
In vitro fertilization by co-incubation or intracytoplasmic sperm injection.
What is Step 2 of PGD?
Harvest one cell from an 8-cell morula.
What is Step 3 of PGD?
Test the harvested cell for known or unknown mutations.
Why can PGD produce false decisions in mosaic embryos?
If the wrong cell is tested, the embryo may be incorrectly classified.
What is PGT-A?
Preimplantation genetic testing for aneuploidy.
What is a major benefit of PGT-A?
Increases efficiency of producing a child.
What is a major drawback of PGT-A?
Cost and potential loss of viable embryos.
How can somatic mosaicism affect paternity or maternity testing?
Different tissues may have different genotypes, causing incorrect test results.
What real-world case illustrates mosaicism affecting maternity testing?
Lydia Fairchild.
Are tortoiseshell and calico cats somatic mosaics?
No, they are mosaic phenotypes due to X-inactivation.
What genetic mechanism causes tortoiseshell coat patterns?
X-linked coat color gene with random X-inactivation.
Is Venus the cat a somatic mosaic or mosaic phenotype?
Somatic mosaic.
What must you know for the exam from this lecture?
Differences between mosaic phenomena, how to interpret testing data, and which techniques can or cannot detect somatic mosaicism.