18.01.12 Normal variation in the human genome

Question 1

How can normal variation be defined?

Answer 1

Normal genomic variation can be described as genetic variants, which are not associated with an adverse phenotypic effect.

~5% of the human genome is structurally varaible (>1kb) with variation taking numerous forms.

Question 2

What is a heteromorphism?

Answer 2

Normal variant exist which are visible at the resolution of the light microscope, usually involving heterochromatin, but also including euchromatic variants.

These visible variants different in size, morphology or staining properties.

Question 3

What proportion of the genome is constitutive heterochromatin? What are its properties?

Answer 3

~6.5% (200Mb) of the human genome
Darkly stained by C-banding
Consists of largely AT-rich genetically inert satellite DNA.
Can vary in length
High copy number tandemly repeated non-coding DNA (100kb) known as satellite DNA.

Question 4

What are the properties of facultative heterochromatin?

Answer 4

Can be either active (decondensed) or inactive (condensed) e.g. Xi in females.

Question 5

Give four examples of normal constitutive heterochromatin variants.

Answer 5

1qh
9qh
16qh
Yqh

1, 9, 16 vary due to inversions of the heterochromatin - most common is the placement of the 9q heterochromatin into 9p immediately adjacent to the centromere.

Yqh may vary due to translocations or insertions

Question 6

What causes variation in the amount of constitutive heterochromatin?

Answer 6

Instability to satellite DNA

Question 7

Are there any clinical implications of chromosomal heteromorphisms?

Answer 7

May have relevance in infertility and spontaneous abortion.