MOL BIO LEC: INHERITED DISEASES

Mutations

are changes in DNA nucleotide sequences?

Mutations

These changes range from single base pair or point mutations of various types to chromosomal.

Silent mutation

change the nucleotide but the equivalent protein is not?

Missense mutation

change the nucleotide, change the equivalent protein as well?

Nonsense mutation

change the nucleotide, change protein into stop codon?

Duchenne Muscular Dystrophy

example of Nonsense mutation

Frameshift mutation

insert, move or shift the sequence ; different read in every codon?

Tay Sach's disease

Example of Frameshift mutation

Cystic fibrosis

example of Frameshift deletion

Autosomal dominant

a child of an affected individual and an unaffected mate has a 50% to

100% risk or likelihood of expressing the disease phenotype (Fig.

12.2)?

ABO blood group

Codominant offspring example?

p53

Dominant-negative example

Autosomal recessive

is the largest category of Mendelian disorders.

Autosomal recessive

The recurrence risk is 25% if siblings are affected, indicating the

presence of mutation in both of the parents?

Autosomal recessive

are more often observed due to two individuals heterozygous for the same mutation-producing offspring?

X-linked inheritance

Almost all sex-linked disorders are _________ because relatively few

genes are on the Y chromosome.

1691 A --> G R506Q

Mutation in Leiden?

F5

Gene in Factor V Leiden that is affected?

1q23

Chromosome in Factor V Leiden that is affected?

4% to 8%

0.06% to 0.25%

In Factor V Leiden

This genotype is heterozygous in _______ of the general population,

and ______ is homozygous for this mutation.

Factor V Leiden

A blood clot or deep venous thrombosis is treated with

anticoagulants?

PCR Methods

PCR-RFLP

PCR with sequence-specific primers

Molecular methods used in detecting Factor V Leiden mutation?

Exon 10

What mutation in Factor V Leiden?

Hemochromatosis

An autosomal-recessive condition that causes overabsorption of iron

from food?

type I HFE or HLA-H

Dysfunction of the hemochromatosis ____________ gene product.

C282Y

The most frequently observed mutation in hemochromatosis is?

Exon 4

What mutation in Hemochromatosis?

Cystic fibrosis

is a life-threatening autosomal-recessive disorder that

causes severe lung damage and nutritional deficiencies?

Cystic fibrosis

Normally, these secretions are thin, but in _________, a defective gene causes the secretions to become thick and sticky.

CFTR gene

Cystic fibrosis is caused by loss of function of the CF transmembrane conductance regulator, the________?

3-bp deletion

phenylalanine

508

The first and most frequently observed mutation in CFTR is a _________ that removes a __________ residue from position ____ of the protein?

Fragile X syndrome

is associated with a triplet-repeat (CGG) expansion in the noncoding region 5′ to the fragile X mental retardation gene, FMR-I?

more than 2,000 CGG

The expansion becomes so large in full fragile X syndrome (_____________ repeats) that the region is microscopically visibl

FMR-1

The CGG repeat expansion 5′ to the gene also results in

methylation of the region and transcriptional shutdown of _____?

PCR, Southern blotting

What molecular methods is used to detect Fragile X syndrome?

Hungtington's disease

Associated with expansion within the huntingtin structural gene

4p16.3

What is huntingtin structural gene?

9 to 37 repeats

38 to 86

Hungtington's disease

In this repeat expansion, the sequence CAG expands from

___________ to ____________in the huntingtin gene

glutamine

The triplet expansion inserts multiple ________ residues in the 5′ end of the huntingtin protein.

hungtington's disease

This causes the protein to aggregate in

plaques, especially in nervous tissue, causing the neurological

symptoms seen in this disease.

Fragile XE

What disorder?

(Xq28)

Friedreich ataxia

What disorder?

(9q13)

Myotonic Dystrophy

What disorder?

9q13.2-13.3)

Spinocerebellar ataxia type 8

What disorder?

(13q21)

Spinocerabral ataxia type 12+

(5q31-33)

amyotrophic lateral sclerosis (ALS), frontotempoeal disorder?

What disorder?

(9p21.1)

GCC

What repeat in Fragile XE?

GAA

What repeat in Freidreich ataxia and Spinocerebellar ataxia type 8?

CTG

What repeat in Myotonic dystrophy?

CAG

What repeat in Spinocerebellar ataxia type 12?

GGGGCC

What repeat in amyotrophic lateral sclerosis (ALS), frontotempoeal disorder?

6-35 (over 200)

Expansion of Fragile XE?

7-34 (over 100)

Expansion of Freidreich ataxia?

5-37 (over 50)

Expansion of Myotonic dystrophy?

16-37 (110-250)

Expansion of spinocerebellar ataxia type 8?

7-28 (66-78)

Expansion of spinocerebellar ataxia type 12?

Exapnsion of amyotrophic lateral sclerosis (ALS), frontotempoeal disorder?

2-20 over (100)