Genetic Analysis: Epigenetics, Population Genetics, Gene Therapy

Epigenetics Definition

The study of how gene expression changes throughout inheritance

What are the 3 main mechanisms of epigenetics?

Reverse modifications, chromatin remodeling, regulate gene expression

Reverse modifications

adding or taking away methyl groups bonded to DNA. Methylated DNA prevents transcription

Chromatin remodeling

adding/removing/altering histones. Altering includes acetylation (open chromatin), and deacetylation (close chromatin)

Regulating gene expression for epigenetic control

done through short and long noncoding RNA which will inhibit transcription or translation

What’s the difference between long and short ncRNA?

short or microRNA interferes with transcription. Long ncRNA covers the chromosome (ex. in X inactivation the X chromosome is completely covered in lncRNA)

Methylome

a set of methylated nucleotides

Why is Pradi-Walis an epigenetic disease?

Because normally we rely on the paternal allele, so the maternal allele is imprinted (silenced). But the paternal allele is lost, and maternal allele is already silenced, so lose entire function of that gene, causing disease.

Genetic imprinting

Involves permanently silencing an allele (either maternal or paternal)

Monoallelic gene expression

when only one allele is expressed (transcribed). Normally results from imprinting

What is Beckwith-Wiedemann syndrome?

Epigenetic, imprinting. Normally have complimentary imprinting caused by methylation pattern. Methylation pattern changes to cause different imprinting pattern.

Examples of random monoallelic expression

X inactivation or randomly imprinting an autosomal gene

Epimutation

changing of expression through changing methylation patterns

What type of methylation pattern do cancer cells have?

they have less methylation (hypomethylation), therefore less regulation

Why might hypomethylation be good in cancer cells?

Increased expression of tumor suppressor genes

Are epigenetic patterns inherited?

Yes. Shown in mice where the coat color is controlled by expression pattern in gene. More expression = more yellow color

What exactly is a dominant mutation? What makes it dominant?

When it is a gain of function mutation. Produces a new, working product with a new function because of the mutation.

How do you calculate the risk factor of genetic diseases?

do a punnent square and remember that when its AND, multiple individual probabilities