Mammalian Genetics

Human life, from a chromosomal viewpoint

X inactivation provides a mechanism for dosage compensation

Females with extra X chromosomes are often normal or nearly normal, due to X inactivation

Mosaics and chimeras

Turner syndrome - 45, X or 46, X, abn X

More Turner…

Why does Turner syndrome occur at all, since only one X chromosome is normally active?

The ovary undergoes programmed destruction of its major product, eggs.

Turner syndrome oocytes virtually gone by the age of 2 years

Klinefelter syndrome - 47, XXY

XYY syndrome

XX males

Biallelic genes can result in monoallelic expression

Biallelic genes can result in monoallelic expression (cont.)

X-chromosome inactivation and imprinting are epigenetic phenomena

The Lyon Hypothesis, after Mary Lyon, a British geneticist, in 1961

Calico cat

Curious X-inactivation facts about calico cats

X inactivation

X inactivation features

Nonrandom X inactivation occurs in female DMD patients with Xp21-autosome translocations

Timing of X inactivation

X inactivation or see below

Blocks of sequence homology between X and Y chromosomes suggest a common origin

X and Y chromosomes show several regions of homology in addition to the common pseudoautosomal regions

Mammalian pseudoautosomal regions have not been well-conserved during evolution

Genes on the Y chromosome:

Some genes escape X inactivation

X chromosome inactivation in marsupials is different

Mammalian phylogeny

Escape from inactivation ensures dosage compensation between XX females and XY males for X-linked genes that have functional Y chromosome counterparts

Differences between XO human and XO mouse

Mapped Turner gene by localizing on the human Y chromosome

X-inactivation seems to occur from an inactivation center

XIST gene, encoded at site of X inactivation center:


Methylation may provide mechanism

Xist (mouse) and XIST (human)


Xist continued…

Models for Xist action

Xist mechanisms

Tsix and Xist have a yin and yang relationship

DNA methylation is essential to maintain X chromosome inactivation

The phenomena of X inactivation and imprinting are associated

Genomic imprinting

Imprinting is a phenomenon whereby the activity of some genes depends on the gender of origin

Mechanism of imprinting not clear

Genomic imprinting requires erasure of the imprint in the germline:

Certain genes are imprinted; Imprinted gene clusters

Parthenogenesis: development without male genome

Parthenogenetic embryos derived from activated eggs develop to blastocyst stage, then die

Can remove nucleus and replace with another nucleus in fertilized eggs, making diploid, using different mouse strains so not homozygous lethal

Embryos die in a complementary syndrome:


Features of imprinting

Models - still unresolved, no evidence

The Ontogeny of the gametic imprint

Mechanisms for imprinted gene silencing

Imprinting in the Prader-Willi and Angelman syndrome region:

Human syndromes that show imprinting effects

AS and PWS differing symptoms:

Expression and Function of imprinted genes,
maternally expressed:

Imprinting may be involved in the Philadephia chromosome

Fragile X - imprinting effects

There is also preferential expansion in males of the repeat associated with Huntington's disease.

H19 and Igf2

List of phenomena that are associated with inheritance from one or another parent