GENETIC FINAL

cancer

define = uncontrolled division of abnormal cells

apoptosis = PCD

maintain homeostasis

when damaged beyond repair, virus, stress, DNA damage 

loss of apoptotic control can lead to cancer

apoptosis morphology 

• discontinuous nuclear envelope
• condensation/shrink
• blebbing 
• DNA fragmentation = karyorrhexis
• apoptotic bodies - phagocytosis

necrosis 

• swelling
• smooth plasma membrane 
• disintegration/membrane rupture
• cell lysis 

cancer major changes 

• immortalization
• transformation/proliferation
• angiogenesis 
• metastasis 
• evasion of apoptosis 
• genetic instability 

influential factors

• environment
• reproductive life 
• lifestyle
• virus
• mutagenic 
• defect in DNA replication

hallmarks

• evading growth suppressor
• avoiding immune destruction
• enabling replicative immortality 
• tumor promoting inflammation
• activating invasion & metastasis 
• inducing angiogenesis 
• genome instability & mutation
• resisting cell death
• deregulating cellular energetics
• sustaining proliferative signaling 

normal cells

• need external signals 
• respond to inhibitory signals
• undergo apoptosis 
• shorten telomere
• depend on blood vessel
• no metastasis 
• cannot grow in low serum
• flat & extend
• anchorage dependence
• exhibit contact inhibition 

cancer cells

• angiogenesis 
• round
• anchorage dependence
• fail to exhibit contact inhibition 

oncogene dominant gain of fx 

proto oncogene (normal gene) 

tumor suppressor gene recessive loss of fx

Knudson's: 2 recessive = carcinogenesis = recessive mutation

haploinsufficiency = 1 allele mutated = express cancer phenotype

metabolism 

inborn errors of met AR or XR

carb:

PKD - PKLR 1q22

G6PD - XR

lactose intolerance - lactase, LCT

aa:

alkaptonuria - AR, homogentisate oxidase, HGD 

PKU - phenylalanine hydroxylase, PAH

albinism - tyrosinase, no melanin, TYR/HPS/CH

maple syrup urine - AR, DBT 

lipid:

Gaucher - glucocerebrosidase

Tay sac - beta hexosaminidase A

familial hypercholesterolemia - LDLR

urea:

hyperammonemia + arginase, argininosuccinate synthetase/lyase 

congenital - 

Type 1 - AR, carbamoyl phosphate synthetase 

Type 2 - XR, ornithine transcarbamoylase

Type 3 - AR

N acetyl glutamate synthetase deficiency - low CPS 1

acquired

SAQ

Dr suhaili

1. many genetic ds disabling/fatal still common, will recessive allele which is lethal in homozygous condition completely removed from a large population? elaborate factor involved with ds example

no 

presence of carrier 

achromatopsia 

Aa x Aa (AA is lethal) 

50% carrier

pass genes to offspring

2. relationship between ... that are able to change allele fx of a genetic ds 3%

bottleneck effect = drastic reduction in population - reduce diversity - 天灾

founder effect = small group isolated from main population - reduce diversity - migration

genetic drift = change in allele frequency from gen to gen due to chance 

natural selection = higher fitness higher survival

non random mating = choose partners based on specific traits 

3. how are chromosome ds been diagnosed 2%

karyotyping, fluorescence in situ hybridization FISH

4. 2 approach looking at susceptible gene for complex ds 4% - strategies for cloning a ds gene

functional cloning - when know biochemical basis of ds - gene encode for enzyme/protein that deficient in disease 

candidate gene - when able to guess what gene might be and test it directly in patients 

positional cloning - when know disease gene's location in genome 

5. write fully interpret reports for following 8%

a. 45, X/46, XX female recurrent miscarriage history

Turner syndrome with 45, X/46, XX mosaicism

b. 46, XX, del (14) (q23)

female with 46 chromosome with deletion on chromosome 14 long arm of band 23

c. 46, XY, dup (14) (q22q25)

male with 46 chromosome with duplication on chromosome 14 long arm of band 22 and 25

d. 46, XX, r (7) (p22q36)

female with 7 ring chromosome

the end of p arm of band 22 fuse with the end of q arm of band 36

6. allele frequency 

p + q = 1

genotype frequency 

p2 + 2pq + q2 = 1

f (WW)=p2=6/9=0.67

f (Ww)=2pq=1/9=0.11

f (ww)=q2=2/9=0.22

f (W)=p= (2(WW) + Ww)/2 (9) = 0.72

f (w)=q=0.28

Lod score 

non recombinant: 8

recombinant: 2

recombinant factor = 2/10 = 0.2 = Θ

Z=0.837 = not linked 

Z more than 3 = linked

Z less than -2 = not linked 

Z = -2 ~ 3 need more data 

genetic mapping - suhaili

3 types of map

• cytogenetic
• linkage
• physical

5 molecular markers

• restrictive fragments length polymorphism = southern blot 
• amplified fragment length polymorphism = PCR technique
• minisatellites & microsatellites = STR/SSR & VNTR
• single nucleotide polymorphism = missense 
• sequence tagged site 

map molecular markers with linkage mapping & LOD mapping 

human development

1 pre embryonic period 2w

2 embryonic period 3-8w

3 fetal period 9- ~37w

regional specification: different pattern from initial similar cell population - form several region 

- gastrulation, neurulation, axis specification 

growth: complex interplay of hormone, nutrient, genes

morphogenesis: change in cellular shape 

cell differentiation: stem cell differentiate to differ fx 

 vs cell determination?

• gene
• signaling molecules
• CAM
• ECM
• cytoskeleton

holoprosencephaly: SHH, signaling molecules, growth - regional specification 

achondroplasia/hypo, thanatophoric dysplasia : FGFR, signaling molecules, growth or morphogenesis 

Duchenne muscular dystrophy: DMD, growth or morphogenesis

Alzheimer's/HTT, neuroblastoma, colon & small cell lung carcinoma: REST, zinc finger gene, differentiation

sympolydactyly: HOXD13, homeobox gene, morphogenesis

hand foot genital syndrome: HOXA13, homeobox gene

male sexual reversal (XY female): SOX9, HMG gene

define morphogen: 2%

substance that governs pattern of tissue development in morphogenesis 

sonic hedgehog SHH

fibroblast growth factor FGF

Dr deming

factors contribute: 4%

lifestyle - nutrients switch on or off certain gene expression - obesity - healthy diet silent lipogenic gene

habits - smoking - damage DNA, promote tumor growth 

socio economic 

geographic location

define heritability: 6%

proportion of observed variability in a trait within a population attribute from genetic differences among these individuals 

genetic contribution to multifactorial trait 

how to study:

low (0.0) = environment factor

high (1.0) = genetic play role in trait 

single gene ds

• clear family history
• early onset
• rare
• high accuracy for predict risk
• all cells 
• germline mutation - embryonic stage
• cystic fibrosis 

multifactorial ds

• long exposure to environmental factors 
• common
• specific cells 
• somatic cell mutation
• cancer

bioethics 2 question 

values: 

autonomy - patient has rights to refuse treatment

beneficence - practitioner should act in best interest of patient

non maleficence - "first, do no harm"

justice - for resource distribution, decision

dignity - way of treating patient & practitioner

truthfulness & honesty - informed consent required

why genetic interesting:

identify risk that not yet affect patient

about families as well as individuals 

genetic research is commercially driven to a substantial degree

issue of genetic testing: 

risk of being tested - psychological - bad gene positive: genetic determinism = possible overestimate of likelihood will suffer/become afflicted; negative: survivor guilt - overconfident no disease

public conceptions of genetics - beliefs - genetic determinism = idea of particular gene = particular trait 

confidentiality & consent & duty to warn 

commodifying genes - for commercialization - Myriad genetics holds patent on BRCA1&2 - insist only they can perform test for BRCA mutation