Lecture 8 BB1035 C15.pptx

7/24/2019 Lecture 8 BB1035 C15.pptx

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What Are Mutations?

Gene Mutations and Molecular Medicine

- Alteration of one allelic form

of a gene to another.

- Genetic mutations: changes in

DNA that are heritable.

Transmittal: (tissue affected

- somatic !s. germinal

"ecture # $ Molecular Medicine


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Chromosomal (larger DNA sequences)


MUTATIONS

Point (a single nucleotide)


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Mutational %ffect

Acti!it& reduced

or eliminated

No!el or increased

Acti!it&



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'ilent: no change in amino acid

Missense: changes a single amino acid


)*NT mutations


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Nonsense: induces sto+ codon

,ram-eshift: addition or deletion changes

amino acid seuence


)*NT mutations


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/0)M)')MA" mutations

ancer cell



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/o1 are DNA molecules

and mutations anal&2ed?0estriction en2&mes:

molecular scissors

Gel electro+horesis:

se+arate nucleic acids b&

si2e



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com+arati!e genomics $ genome +ros+ecting

'ingle nucleotide

ol&mor+hism ('N:

DNA !ariation

3 45 of +o+ulation

675 of !ariation

89 -T

0estriction fragment length

ol&mor+hism (0,":

alters restriction site

use for allelic genot&+ing lin;age to disease

What DNA changes lead to genetic diseases?

b. correlate 1ith

s+ecific

diseases

c. identif& molecular

basis for

disease GG e=+ansion@ mental retardation -BC 1t BB-877 +remutation

877-8777 disease ,M0-4 BET0 binds m0NAs in neurons

8. >-lin;ed muscular atro+h& AG e=+ansion (/untingtons 84 1t C7-B8 disease

disru+t androgen rece+tor )0,

. m&otonic d&stro+h& TG e=+. B 1t B7 mild disease

4777 se!ere disease ET0 (noncoding effect

Wild t&+e (WT

+remutated

diseased

/o1 do defecti!e

genes9+roteins lead todiseases?



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b. 'euence e=+ansions $ tri-nucleotide re+eats

/o1 do defecti!e genes9+roteins lead to diseases?

Three children - B75 ris; to inherit/untington disease from their father.

Case Study

genetests!org

1t

+remutated

diseased



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b. 'euence e=+ansions $ trinucleotide re+eats

/o1 do defecti!e genes9+roteins lead to diseases?

4. Do the& ha!e different ris;s for de"elo#ingdisease?

Case Study genetests!org

$%& ' disease *+ ' reduced #enetrance

,-*. ' not at ris/

henot&+es de+endent on s+ecific mutation

res&m+tomatic testing 0esources



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c. Deletions: large@ small - in frame !s. out of frame0ene structure

1 ,!m23 -+ e4ons3

1 5%/2 m6NA

1 758&&& 9 :hy;

1 DMD ' amor#hic (out

o<


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a. +renatal@ ne1born@ adults (as&m+tomaticF

b. testing - DNA@ +rotein@ metabolites

1t

mt

carrier

/o1 *s Genetic 'creening Esed to Detect Diseases? (38777

a. restricting substrate $ E@ limit +hen&lalanine

b. metabolic inhibitors $ statins $ bloc; cholesterol

c. gene thera+& $ restore gene function

d. directed thera+eutics (biologics9small molecules

/o1 are Genetic Diseases Treated?



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c. gene thera+& $ restore gene

function (3677 trials


Gene therapy vectors

adeno!irus

retro!irus



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c. gene thera+& $ restore gene function (3677 trials




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c. gene thera+& $ restore gene function (3677 trials




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Gene classes

Diseases


Lecture 8 BB1035 C15.pptx

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