Genetics Exam Ii Genetic Anticipation

Front 1

Increased frequency of affected relatives, increased severity of phenotype, or earlier age of onset in successive generations.

Back 1

Genetic Anticipation

Front 2

Most common inherited form of mental retardation

Back 2

Fragile X syndrome

Front 3

What type of inheritance is Fragile X syndrome?

Back 3

x-linked recessive

Front 4

Phenotype of X-linked recessive

Back 4

You have large head, large ears, larger testis, and mental retardation

corrleated with autism.

Front 5

If a male or a female has developmental delay what should the doc do?

Back 5

1. Chrom. analysis

2. DNA test for fragile X

Front 6

Sherman Paradox in Fragile X

Back 6

Mental retardation seemed to worsen with each successive generations, anticipation

Front 7

Sherman suggested "premutation"

Back 7

This suggests that something is happening to transform that affected gene into a full mutation, whereas earlier on it was less affected.

Front 8

Nucleotide repeat expansion

Cause for Fragile X

Expansion of CGG in promoter of 5'end.

Back 8

Normal individuals have ~40 repeats

Premutation individuals have ~40-200 repeats

If pass on, repeats likely to increase to 200+. Region is methylated-->deactivates promoter-->silent gene-->no production of protein-->affected

Front 9

Why are carrier females carrying full mutation affected or not affected?

Back 9

1. Maybe they are (soft signs of phenotype)

2. X-inactivation of mutant X chromosome

3. Delayed onset

Front 10

New clinical entities relative to the FMR-1 locus

Ovarian Failure

Back 10

1. Females with premutations of the FMR-1 gene are at an inc. risk for premature ovarian failure

Women with full FMR-1 mutations are not affected

the length of the trinucleotide expansion determines this risk

Front 11

New clinical entities relative to the FXTAS

Back 11

Males who have trinucleotide repeats less than 200 tend to develop neurological problems

Still produce gene product, but RNA is abnormal because of the premutation expansion

Front 12

What are the two subclasses of trinucleotide repeat disorders?

Back 12

1. Those that have repeats in non-coding regions of a gene

2. Those repeats that are in the coding regions

Front 13

Myotonic Dystrophy

Back 13

Muscle keeps on contracting when want it to relax.

Nucleotide repeat expansion occurs in the 3' end of the untranslated region, codes for myotonin-protein kinase.

DMPK protein levels unaffected (like Fragile X), problem with the expanded RNA and its processing.

Front 14

Another class of trinucleotide repeat disorder in which repeats are in a coding region of an autosomal gene

Back 14

-Result in polyglutamines being incorporated.

Example: Huntington disease

Front 15

Huntingtons Disease

Back 15

-Motor, cognitive, and psychiatric disturbances

-10% of patients with onset before age 20. Increased expansion means earlier age of onset.