GENETICA
CONTENTS
historisch perspectief .................................................................................................................................................. 3
wetten van mendel ................................................................................................................................................... 3
dom vs rec ............................................................................................................................................................ 3
homozyg vs heterozyg vs hemizyg .......................................................................................................................... 3
codom en onvolledige dom.................................................................................................................................... 3
stambomen ............................................................................................................................................................. 3
cytogenetica ........................................................................................................................................................... 3
humaan genoom .......................................................................................................................................................... 4
gen variatie .............................................................................................................................................................. 4
celcyclus ................................................................................................................................................................. 4
chr onderzoek .......................................................................................................................................................... 5
karyotypering ........................................................................................................................................................ 5
ideorgam .............................................................................................................................................................. 5
genotype fenotype ................................................................................................................................................ 5
numerieke chromosomale defecten: trisomie 21........................................................................................................ 5
homologe chr vs zusterchromatiden .......................................................................................................................... 6
spermatogenese ...................................................................................................................................................... 6
oogenese ................................................................................................................................................................. 6
numerieke chromosomale defecten .......................................................................................................................... 6
structurele chromosomale afwijkingen ...................................................................................................................... 7
translocaties ........................................................................................................................................................ 7
subtelomerische deleties .................................................................................................................................... 7
segmentele duplicatie ......................................................................................................................................... 8
genomische afwijkingen........................................................................................................................................... 8
cytogenetisch onderzoek ......................................................................................................................................... 8
molec genetica: chr gen ........................................................................................................................................... 8
genetische varianten ................................................................................................................................................ 9
single nucleotie variants = cnv............................................................................................................................. 9
indels ................................................................................................................................................................ 10
microsatellite repeats – short tandem repeats (STR) ......................................................................................... 10
nomenclatuur: HGVS ............................................................................................................................................. 10
gDNA ................................................................................................................................................................. 10
cDNA ................................................................................................................................................................. 10
eiwit ................................................................................................................................................................... 10
c notatie ............................................................................................................................................................ 11
oef ..................................................................................................................................................................... 11
variant disease ...................................................................................................................................................... 11
, causale varianten .................................................................................................................................................. 12
classificatie van varianten ....................................................................................................................................... 12
overerving.................................................................................................................................................................. 12
complicating factors - niet-mendeliaanse overerving ................................................................................................ 12
geslachtsgebonden overerving ................................................................................................................................ 13
lyonizatie of X chr inactivatie ............................................................................................................................. 13
x gebonden rec overerving .................................................................................................................................. 13
y gebonden overerving ........................................................................................................................................ 13
onvolledige penetrantie..................................................................................................................................... 14
variabele expressie ........................................................................................................................................... 14
locus heterogeniteit .......................................................................................................................................... 14
triplet repeats – dyn mutaties ............................................................................................................................ 14
imprinting .......................................................................................................................................................... 14
mt en mtDNA mt genoom ................................................................................................................................ 14
kankergenetica .......................................................................................................................................................... 15
kANKER SUBGROEPEN ........................................................................................................................................... 16
CARCINOMAS .................................................................................................................................................... 16
leukemia ........................................................................................................................................................... 16
lymphomas ....................................................................................................................................................... 16
carcomas .......................................................................................................................................................... 16
kankergenetica....................................................................................................................................................... 16
verstoorde cellulaire processen bij kanker ......................................................................................................... 16
kanker = genetische aandoening .......................................................................................................................... 16
genen betrokken bij kanker ................................................................................................................................. 17
molec therapie .................................................................................................................................................. 18
biomerkers ........................................................................................................................................................ 18
populatiegenetica ...................................................................................................................................................... 18
allel- en genotypefreq ............................................................................................................................................. 18
genomics toekomst ............................................................................................................................................... 19
genoom in kaart brengen......................................................................................................................................... 19
next generation genetics ....................................................................................................................................... 20
, HISTORISCH PERSPECTIEF
Genetica meestal toevallig ontdekt
Vroeger ontstaan mens: mini mens in spermacel, eicel = voeding (animalkulism), mini mens in eicel (ovisme)
Charles Darwin: eicel en spermacel belangrijk => overerving van kenmerken
Kleine deeltjes (gemmules) van uiterlijke kenmerken in eicel/spermacel
Nature: genen <-> nurture: opvoeding + omgeving => realiteit = mix
WETTEN VAN MENDEL
1. Uniformiteitswet: 2 homozyg met 1 versch kenmerk => nakomelingen gelijk
2. Splitsingswet: kruising F1 => versch fenotypen in F2 met 3:1 verhouding (dom-rec)
3. Onafhankelijkheidswet: kenmerken = onafh overgeerfd
DOM VS REC
Dom = altijd tot uiting als aanwezig
Rec = niet tot uiting bij aanwezigheid van dom, wel als 2 rec
Bij mens: nooit simpel, nooit 1 gen => wel belangrijk bij ziektes
HOMOZYG VS HETEROZYG VS HEMIZYG
Homozyg = 2 dez allelen
Heterozyg = 2 versch allelen
Hemizyg = 1 allel (vb: X chr bij mannen)
CODOM EN ONVOLLEDIGE DOM
Mendel: volledige dom
Onvolledige dom = intermed = semidom = incomplete dom = mengtype
Codom (vb: bloedgroep AB) beide fentotypes
STAMBOMEN
Cosanguiniteit = bloedverwantschap
Enkel mannen hebben aandoening = X gebonden
Uitzonderingen:
Dom kenmerk kan in zaadcel van vader ontwikkelen = de novo mutatie
Onvolledige penetrantie = drager zijn van dom kenmerk die niet tot uiting komt
CYTOGENETICA
= onderzoek van chromosomen tijdens celdeling
Meiose
Chromosomale basis van geslacht => X en Y chr (fruitvliegjes/drosophilia)
CONTENTS
historisch perspectief .................................................................................................................................................. 3
wetten van mendel ................................................................................................................................................... 3
dom vs rec ............................................................................................................................................................ 3
homozyg vs heterozyg vs hemizyg .......................................................................................................................... 3
codom en onvolledige dom.................................................................................................................................... 3
stambomen ............................................................................................................................................................. 3
cytogenetica ........................................................................................................................................................... 3
humaan genoom .......................................................................................................................................................... 4
gen variatie .............................................................................................................................................................. 4
celcyclus ................................................................................................................................................................. 4
chr onderzoek .......................................................................................................................................................... 5
karyotypering ........................................................................................................................................................ 5
ideorgam .............................................................................................................................................................. 5
genotype fenotype ................................................................................................................................................ 5
numerieke chromosomale defecten: trisomie 21........................................................................................................ 5
homologe chr vs zusterchromatiden .......................................................................................................................... 6
spermatogenese ...................................................................................................................................................... 6
oogenese ................................................................................................................................................................. 6
numerieke chromosomale defecten .......................................................................................................................... 6
structurele chromosomale afwijkingen ...................................................................................................................... 7
translocaties ........................................................................................................................................................ 7
subtelomerische deleties .................................................................................................................................... 7
segmentele duplicatie ......................................................................................................................................... 8
genomische afwijkingen........................................................................................................................................... 8
cytogenetisch onderzoek ......................................................................................................................................... 8
molec genetica: chr gen ........................................................................................................................................... 8
genetische varianten ................................................................................................................................................ 9
single nucleotie variants = cnv............................................................................................................................. 9
indels ................................................................................................................................................................ 10
microsatellite repeats – short tandem repeats (STR) ......................................................................................... 10
nomenclatuur: HGVS ............................................................................................................................................. 10
gDNA ................................................................................................................................................................. 10
cDNA ................................................................................................................................................................. 10
eiwit ................................................................................................................................................................... 10
c notatie ............................................................................................................................................................ 11
oef ..................................................................................................................................................................... 11
variant disease ...................................................................................................................................................... 11
, causale varianten .................................................................................................................................................. 12
classificatie van varianten ....................................................................................................................................... 12
overerving.................................................................................................................................................................. 12
complicating factors - niet-mendeliaanse overerving ................................................................................................ 12
geslachtsgebonden overerving ................................................................................................................................ 13
lyonizatie of X chr inactivatie ............................................................................................................................. 13
x gebonden rec overerving .................................................................................................................................. 13
y gebonden overerving ........................................................................................................................................ 13
onvolledige penetrantie..................................................................................................................................... 14
variabele expressie ........................................................................................................................................... 14
locus heterogeniteit .......................................................................................................................................... 14
triplet repeats – dyn mutaties ............................................................................................................................ 14
imprinting .......................................................................................................................................................... 14
mt en mtDNA mt genoom ................................................................................................................................ 14
kankergenetica .......................................................................................................................................................... 15
kANKER SUBGROEPEN ........................................................................................................................................... 16
CARCINOMAS .................................................................................................................................................... 16
leukemia ........................................................................................................................................................... 16
lymphomas ....................................................................................................................................................... 16
carcomas .......................................................................................................................................................... 16
kankergenetica....................................................................................................................................................... 16
verstoorde cellulaire processen bij kanker ......................................................................................................... 16
kanker = genetische aandoening .......................................................................................................................... 16
genen betrokken bij kanker ................................................................................................................................. 17
molec therapie .................................................................................................................................................. 18
biomerkers ........................................................................................................................................................ 18
populatiegenetica ...................................................................................................................................................... 18
allel- en genotypefreq ............................................................................................................................................. 18
genomics toekomst ............................................................................................................................................... 19
genoom in kaart brengen......................................................................................................................................... 19
next generation genetics ....................................................................................................................................... 20
, HISTORISCH PERSPECTIEF
Genetica meestal toevallig ontdekt
Vroeger ontstaan mens: mini mens in spermacel, eicel = voeding (animalkulism), mini mens in eicel (ovisme)
Charles Darwin: eicel en spermacel belangrijk => overerving van kenmerken
Kleine deeltjes (gemmules) van uiterlijke kenmerken in eicel/spermacel
Nature: genen <-> nurture: opvoeding + omgeving => realiteit = mix
WETTEN VAN MENDEL
1. Uniformiteitswet: 2 homozyg met 1 versch kenmerk => nakomelingen gelijk
2. Splitsingswet: kruising F1 => versch fenotypen in F2 met 3:1 verhouding (dom-rec)
3. Onafhankelijkheidswet: kenmerken = onafh overgeerfd
DOM VS REC
Dom = altijd tot uiting als aanwezig
Rec = niet tot uiting bij aanwezigheid van dom, wel als 2 rec
Bij mens: nooit simpel, nooit 1 gen => wel belangrijk bij ziektes
HOMOZYG VS HETEROZYG VS HEMIZYG
Homozyg = 2 dez allelen
Heterozyg = 2 versch allelen
Hemizyg = 1 allel (vb: X chr bij mannen)
CODOM EN ONVOLLEDIGE DOM
Mendel: volledige dom
Onvolledige dom = intermed = semidom = incomplete dom = mengtype
Codom (vb: bloedgroep AB) beide fentotypes
STAMBOMEN
Cosanguiniteit = bloedverwantschap
Enkel mannen hebben aandoening = X gebonden
Uitzonderingen:
Dom kenmerk kan in zaadcel van vader ontwikkelen = de novo mutatie
Onvolledige penetrantie = drager zijn van dom kenmerk die niet tot uiting komt
CYTOGENETICA
= onderzoek van chromosomen tijdens celdeling
Meiose
Chromosomale basis van geslacht => X en Y chr (fruitvliegjes/drosophilia)
