Lecture 14: Mosaicism and Chimerism

Mosaicism

Cells with different genetic complements in an individual derived from one zygote.

Chimerism

Cells with different haploid complements in an individual derived from two separate zygotes.

Mechanisms for twins discordant in sex from a single conceptus

1. Discordant for sex: 47XXY cells in baby A and 46XX cells in baby B

2. Discordant for chromosome complement: 46XY in baby A and 47XY+21 in baby B.

How common is mosaicism?

Very common; we are all mosaic due to accumulated DNA damage and errors over time.

Reasons why mosaicism can increase or decrease over time

Increase if it doesn't impact survival or creates an advantage; decrease if it creates a survival disadvantage.

Also all females mammals are mosaic for XCI

Gynandromorphs

Animals that are half male and half female

Mechanisms underlying gynandromorphs

Can arise from fertilization of an egg and polar body by two sperm

Mutation in sex-determining genes

Mosaicism for sex chromosome complement during early cell divisions

Temperature variation

Can gynandromorphs occur in humans?

Bilateral gynandromorphs don’t arise in humans - we lack bilateral symmetry

But we have disorders of sex development → different phenotypes

Challenges in diagnosing mosaicism

1. Present at low levels

2. Present in only certain cell populations

3. Difficult to detect in hard-to-reach tissues

4. Below the detection level of assay techniques.

Assays results of discordant sex twins

1. Trisomy rescue SNP array

   • twins have same result

   • one is XXY and one is XX → both Xs are same

2. sesqui-zygotic twins SNP array

   • both twins have same maternal allele but different paternal

   • one egg fertilized by 2 sperm

Mother-fetal chimerism

Trafficking of cells between mother and fetus that can remain throughout life at low levels.