• Non-Mendelian Inheritance
• Imprinting  and DNA methylation
• Extranuclear chromosomes

Non-Mendelian Inheritance

Some forms of inheritance complicate the pattern of Mendelian inheritance and reassortment of traits.  Inheritance may be overlaid by expansion of triplet repeats, or by parental imprinting.  A  few genes are not inherited by Mendelian principles at all, because they are contained on an extranuclear chromosome of the mitochondria or chloroplast.

Microsatellite expansion

A well-known example is Fragile X Syndrome.  This very common cause of mental retardation results from a region of repetitive DNA sequence that grows longer than normal with each generation.  The length of the sequence--a multiple triplet repeat, called a microsatellite--encourages the region of the chromosome to shut down expression of an essential FMR1 gene nearby.  It also makes the chromosome "fragile;" that region of the chromosome fails to condense during cell culture for karyotyping.  Fragile X shows incomplete dominance; females who carry the trait will show partial (but not total) compensation by the wild-type allele on the other X chromosome. The effectiveness of the compensation is partly related to patterns of X-inactivation.
Check here for more on Fragile X inheritance.

Imprinting and DNA methylation

So far, all the inheritance mechanisms we have considered depend on DNA sequence of bases: A, T, C, G.  However, certain sequences in addition contain chemical modification such as methylation.  These modifications are added after DNA replication.  They add information about how a gene will be expressed.

In mammals, methylation occurs in the gonads, as sperm or eggs develop.
The male and female produce DIFFERENT patterns of methylation.  This means that the degree of expression of a trait may be different, depending on which parent you have inherited the trait from--even though the trait is completely autosomal.

For example Huntington's disease is autosomal dominant.  The onset of disease may occur in childhood, if you inherit the trait through your father; but only much later in life, if you inherit through your mother.

Another disease involving methylation is Fragile X Syndrome.  (See your handout.)  In Fragile X, a region of repetitive CGG sequence is too long.  The length of the repetitive sequence stimulates enzymes to "turn off" expression, including a nearby essential gene, FMR-1.  This sequence is "turned off" through methylation in the female, and fails to get "turned back on" in her children.  Children of males do not show the syndrome; but the grandchildren have high risk.

Extranuclear Chromosomes

Outside the nucleus are the mitochondria, which evolved out of endosymbiotic bacteria.  Plants in addition have chloroplasts which arose the same way.  Mitochondria  have small circular chromosomes which are inherited through the female, because the sperm contribute no mitochondria to the fertilized egg.

A mother passes on mitochondrial traits to all of her children.  Some Mitochondrial Diseases  have been identified, including muscle degeneration and some forms of migraine headache.