Genetics of Inherited Disease

Question 1

how much of the human genome codes for proteins?

Answer 1

about 3%

lenght of human genome 3X10^9

common CDS: 3000 NT

Question 2

what are some ways that a person could obtain heritable dz? (3)

Answer 2

mutations in single genes = single gene disorders

Variation in genes + enviornment = multifactorial dz

Chromosomal imbalances = chromosome disorders

just because you have a mutation, doesn’t mean the phenotype will show; environment also plays a role

Question 3

Name the mutation:

CGA (arg) > TGA (x)

TCT (Ser) > TCA (Ser)

CAT (His) > CCT (Pro)

AGNNN-NNNGT> ACNNNN-NNNGT

-20T>A

TCAGCC> TAGCC

TCAGCC> TCAACCGCC

CAGCAG> CAGCAGCAGCAG

Answer 3

CGA (arg) > TGA (x) = nonsense

TCT (Ser) > TCA (Ser) = silent

CAT (His) > CCT (Pro) =missense

AGNNN-NNNGT> ACNNNN-NNNGT =splice site

-20T>A =upstream, promoter

TCAGCC> TAGCC =deletion

TCAGCC> TCAACCGCC =insertion

CAGCAG> CAGCAGCAGCAG =repeat

Question 4

what are some types of chromosome mutations

Answer 4

amplification

deletion

translocation (could lead to amp or deletion)

dependings on amount - coudl cause a problem in the next generation

IE) (9,22) philadephial chromsome

ABL originally from 9 –> 11 near BCR

–> misregulation of tyrosine kinase, sets up from INC proliferation ie) amp in CM

amplification, via Her2Newu in breast CA

Deletion, cri-du-chat, chromosome 5 pair (missing!)

Question 5

Complete genome mutations:

What can go wrong in trisomy abnormalities?

what increases the risk?

what are some examples?

Answer 5

Meiotic non-disjunction

• Frequency increases with parental age in mother*
• Trisomy 21/down syndrome,*
• Trisomy 18/Edwards,*
• Trisomy 13/Patau syndrome,*
• Trisomy of sex chromosomes ie) Klinefelter (XXY)*
• Monosomy - Turners (XO)*
• Quadrosomy XXYY*

Question 6

How are cytogenic disorders detected?

Answer 6

Cytogenetics study the structure and function of the chromsomes

FISH to detect chrosomes

Karyotyping (older), will allow you to see both strands and the banding patter allows you to see where the abnl lies

Comparative genomic hybridization CGH analysis (hybridize with 2 geneomes labled with different colors, you could see the lighting up more or less depending its density)

Next-gen sequencing

Question 7

What are different classifications of single gene mutations

Answer 7

Sex linked VS autosomal

Recessive VS dominant

Question 8

Osteogenesis imperfecta is an inherited disease that affects collagen formation.

What type of Osteogenesis Imperfecta involves haploinsufficiency?

what is haploinsufficiency?

Answer 8

Type 1 with a NULL mutation in pro-collagen alpha-1

Haploinsufficiencey = “not enough” on allele is not enough to compensate the loss of the gene product

Question 9

Marfan’s Syndrome:

genetic variation?

sx:

Answer 9

Autosomal Dominant Syndrome

sx: long fingers, cachectic,

Question 10

Familial Hypercholesteroremia (FHA) sx

Answer 10

xandoma of the skin

can’t take into cells