Inleiding tot de genetica
Inhoud
Introductie genetica .......................................................................................................................................... 5
Wat is genetica? .............................................................................................................................................. 5
Het menselijke genoom ................................................................................................................................... 6
1) Mendeliaanse genetica ................................................................................................................................. 8
Mendel’s experimentele opzet ......................................................................................................................... 8
Monohybride kruisingen .................................................................................................................................. 8
Testkruising ..................................................................................................................................................... 9
Recessieve versus dominante mutaties .......................................................................................................... 9
Polymorfismen .............................................................................................................................................. 10
Dihybride kruisingen ...................................................................................................................................... 10
Toepassing van genetica in landbouw............................................................................................................ 10
Kansberekening............................................................................................................................................. 10
2) Aanvullingen Mendel ................................................................................................................................... 11
Onvolledige dominantie ................................................................................................................................ 11
co-dominantie............................................................................................................................................... 11
Overdominantie/ heterozygoot voordeel........................................................................................................ 11
letale allelen.................................................................................................................................................. 12
Recessieve letale allelen ........................................................................................................................... 12
Dominante letale allelen............................................................................................................................ 12
Conditionele letale allelen......................................................................................................................... 12
multipele allelen ........................................................................................................................................... 12
Penetrantie en expressiviteit.......................................................................................................................... 12
Interacties tussen genen en omgeving ........................................................................................................... 13
Polygene overerving – kwantitatieve kenmerken ............................................................................................ 13
Polygene overerving – kwalitatieve kenmerken .............................................................................................. 13
Polygene overerving en ziektes ...................................................................................................................... 13
Genetische basis van gedrag ......................................................................................................................... 13
Interlocus geneffecten .................................................................................................................................. 14
3) Chromosomen ............................................................................................................................................. 16
Geslachtschromosomen............................................................................................................................... 17
geslacht VS gender ....................................................................................................................................... 18
X-gekoppelde afwijking .............................................................................................................................. 18
Genenbalans en doseringscompensatie ....................................................................................................... 19
Genetische mozaïek ...................................................................................................................................... 19
Geslachtsbepaling ........................................................................................................................................ 19
1
, Ongeslachtelijke voortplanting ...................................................................................................................... 19
Mannelijk of vrouwelijk gedrag ....................................................................................................................... 20
Homosexualiteit ............................................................................................................................................ 20
Hybriden ....................................................................................................................................................... 20
Koppeling tussen genen ................................................................................................................................ 20
Stukuitwisseling ............................................................................................................................................ 20
Chiasmata..................................................................................................................................................... 20
Stukuitwisseling ............................................................................................................................................ 21
Recombinatiefrequentie................................................................................................................................ 21
Genkartering ................................................................................................................................................. 21
Volgorde van genen op chromosoom ......................................................................................................... 21
Meervoudige stukuitwisselingen ................................................................................................................ 22
Karteren X chromosoom ............................................................................................................................ 22
Chromosoomkartering bij mens .................................................................................................................... 22
Moleculaire merkers .................................................................................................................................. 22
Genkartering d.m.v. moleculaire merkers .................................................................................................. 23
Genome-wide association studies – GWAS ............................................................................................... 23
Fenotype linken aan gen ................................................................................................................................ 23
Cytoplasmatische aggregatie ........................................................................................................................ 24
Cytoplasmatische overerving ........................................................................................................................ 24
Mitochondriale ‘Eva’ ...................................................................................................................................... 24
Aneuploïdie ................................................................................................................................................... 24
Down syndroom......................................................................................................................................... 25
Aneuploïdie van geslachtschromosomen .................................................................................................. 25
Wijzigingen in chromosoomstructuur ............................................................................................................ 25
Deleties ..................................................................................................................................................... 25
Duplicaties ................................................................................................................................................ 26
Inversie ...................................................................................................................................................... 26
Translocatie ............................................................................................................................................... 27
Robertsonische translocatie ...................................................................................................................... 27
Risico op erfelijke afwijkingen........................................................................................................................ 27
Genetisch advies ........................................................................................................................................... 28
Ethische aspecten van genetische tests ........................................................................................................ 28
Monoploïdie .................................................................................................................................................. 28
Tetraploïdie.................................................................................................................................................... 28
Triploïdie ....................................................................................................................................................... 28
Allopolyploïdie .............................................................................................................................................. 29
4) Mutaties ....................................................................................................................................................... 30
2
, Structuur proteïnen ................................................................................................................................... 30
Genetische code ....................................................................................................................................... 30
Puntmutatie: basenpaarsubstitutie ............................................................................................................... 30
Verschillende mutaties in zelfde gen ............................................................................................................. 31
Temperatuursgevoelige mutatie ................................................................................................................. 31
Puntmutatie: indelmutatie ......................................................................................................................... 31
Eén gen, vele mutante allelen........................................................................................................................ 31
Suppressormutatie .................................................................................................................................... 32
Genetische mozaïek door somatische mutatie .......................................................................................... 32
Kiemlijn versus somatische mutatie .............................................................................................................. 33
Mutaties bij ♂ en ♀ ........................................................................................................................................ 33
De celcyclus bij meercellige organismen....................................................................................................... 33
Regulatie van celcyclus door cyclines ....................................................................................................... 33
Proto-oncogenen ....................................................................................................................................... 33
Tumor-suppressor genen ........................................................................................................................... 33
Tumoren en kanker ........................................................................................................................................ 34
Erfelijke of sporadische retinoblastoma..................................................................................................... 34
Spontane mutaties ........................................................................................................................................ 34
Spontane mutaties: herhalingen ................................................................................................................ 34
.................................................................................................................................................................. 35
Ziekte van Huntington ................................................................................................................................ 35
Geïnduceerde mutaties: chemisch ............................................................................................................... 35
Geïnduceerde mutaties: straling ................................................................................................................... 35
Xeroderma pigmentosum .......................................................................................................................... 35
Herstel thymine-dimeren (UV) ....................................................................................................................... 35
Base excisie herstel ................................................................................................................................... 35
Herstel foute basenparing ............................................................................................................................. 36
6) Populatiegenetica........................................................................................................................................ 37
Wat is populatiegenetica? ............................................................................................................................. 37
Hardy-Weinberg principe ........................................................................................................................... 37
Evolutie ......................................................................................................................................................... 37
niet-willekeurige paring.............................................................................................................................. 38
Genetische drift............................................................................................................................................. 38
Evolutietheorie: Darwin en Wallace, evolutie door natuurlijke selectie .......................................................... 39
Evolutie door natuurlijke selectie: fitness .................................................................................................. 39
Evolutie door sexuele selectie ................................................................................................................... 39
Evolutie in menselijke populaties............................................................................................................... 39
Behoud van variatie ....................................................................................................................................... 40
3
, Behoud van variatie: frequentie-afhankelijke selectie ................................................................................ 40
Behoud van variatie: variabele selectie ...................................................................................................... 40
Behoud van variatie: heterozygoot voordeel............................................................................................... 40
Selectie op continue variatie ......................................................................................................................... 40
Grenzen aan selectie ..................................................................................................................................... 41
Aanwijzingen voor evolutie ............................................................................................................................ 41
4
Inhoud
Introductie genetica .......................................................................................................................................... 5
Wat is genetica? .............................................................................................................................................. 5
Het menselijke genoom ................................................................................................................................... 6
1) Mendeliaanse genetica ................................................................................................................................. 8
Mendel’s experimentele opzet ......................................................................................................................... 8
Monohybride kruisingen .................................................................................................................................. 8
Testkruising ..................................................................................................................................................... 9
Recessieve versus dominante mutaties .......................................................................................................... 9
Polymorfismen .............................................................................................................................................. 10
Dihybride kruisingen ...................................................................................................................................... 10
Toepassing van genetica in landbouw............................................................................................................ 10
Kansberekening............................................................................................................................................. 10
2) Aanvullingen Mendel ................................................................................................................................... 11
Onvolledige dominantie ................................................................................................................................ 11
co-dominantie............................................................................................................................................... 11
Overdominantie/ heterozygoot voordeel........................................................................................................ 11
letale allelen.................................................................................................................................................. 12
Recessieve letale allelen ........................................................................................................................... 12
Dominante letale allelen............................................................................................................................ 12
Conditionele letale allelen......................................................................................................................... 12
multipele allelen ........................................................................................................................................... 12
Penetrantie en expressiviteit.......................................................................................................................... 12
Interacties tussen genen en omgeving ........................................................................................................... 13
Polygene overerving – kwantitatieve kenmerken ............................................................................................ 13
Polygene overerving – kwalitatieve kenmerken .............................................................................................. 13
Polygene overerving en ziektes ...................................................................................................................... 13
Genetische basis van gedrag ......................................................................................................................... 13
Interlocus geneffecten .................................................................................................................................. 14
3) Chromosomen ............................................................................................................................................. 16
Geslachtschromosomen............................................................................................................................... 17
geslacht VS gender ....................................................................................................................................... 18
X-gekoppelde afwijking .............................................................................................................................. 18
Genenbalans en doseringscompensatie ....................................................................................................... 19
Genetische mozaïek ...................................................................................................................................... 19
Geslachtsbepaling ........................................................................................................................................ 19
1
, Ongeslachtelijke voortplanting ...................................................................................................................... 19
Mannelijk of vrouwelijk gedrag ....................................................................................................................... 20
Homosexualiteit ............................................................................................................................................ 20
Hybriden ....................................................................................................................................................... 20
Koppeling tussen genen ................................................................................................................................ 20
Stukuitwisseling ............................................................................................................................................ 20
Chiasmata..................................................................................................................................................... 20
Stukuitwisseling ............................................................................................................................................ 21
Recombinatiefrequentie................................................................................................................................ 21
Genkartering ................................................................................................................................................. 21
Volgorde van genen op chromosoom ......................................................................................................... 21
Meervoudige stukuitwisselingen ................................................................................................................ 22
Karteren X chromosoom ............................................................................................................................ 22
Chromosoomkartering bij mens .................................................................................................................... 22
Moleculaire merkers .................................................................................................................................. 22
Genkartering d.m.v. moleculaire merkers .................................................................................................. 23
Genome-wide association studies – GWAS ............................................................................................... 23
Fenotype linken aan gen ................................................................................................................................ 23
Cytoplasmatische aggregatie ........................................................................................................................ 24
Cytoplasmatische overerving ........................................................................................................................ 24
Mitochondriale ‘Eva’ ...................................................................................................................................... 24
Aneuploïdie ................................................................................................................................................... 24
Down syndroom......................................................................................................................................... 25
Aneuploïdie van geslachtschromosomen .................................................................................................. 25
Wijzigingen in chromosoomstructuur ............................................................................................................ 25
Deleties ..................................................................................................................................................... 25
Duplicaties ................................................................................................................................................ 26
Inversie ...................................................................................................................................................... 26
Translocatie ............................................................................................................................................... 27
Robertsonische translocatie ...................................................................................................................... 27
Risico op erfelijke afwijkingen........................................................................................................................ 27
Genetisch advies ........................................................................................................................................... 28
Ethische aspecten van genetische tests ........................................................................................................ 28
Monoploïdie .................................................................................................................................................. 28
Tetraploïdie.................................................................................................................................................... 28
Triploïdie ....................................................................................................................................................... 28
Allopolyploïdie .............................................................................................................................................. 29
4) Mutaties ....................................................................................................................................................... 30
2
, Structuur proteïnen ................................................................................................................................... 30
Genetische code ....................................................................................................................................... 30
Puntmutatie: basenpaarsubstitutie ............................................................................................................... 30
Verschillende mutaties in zelfde gen ............................................................................................................. 31
Temperatuursgevoelige mutatie ................................................................................................................. 31
Puntmutatie: indelmutatie ......................................................................................................................... 31
Eén gen, vele mutante allelen........................................................................................................................ 31
Suppressormutatie .................................................................................................................................... 32
Genetische mozaïek door somatische mutatie .......................................................................................... 32
Kiemlijn versus somatische mutatie .............................................................................................................. 33
Mutaties bij ♂ en ♀ ........................................................................................................................................ 33
De celcyclus bij meercellige organismen....................................................................................................... 33
Regulatie van celcyclus door cyclines ....................................................................................................... 33
Proto-oncogenen ....................................................................................................................................... 33
Tumor-suppressor genen ........................................................................................................................... 33
Tumoren en kanker ........................................................................................................................................ 34
Erfelijke of sporadische retinoblastoma..................................................................................................... 34
Spontane mutaties ........................................................................................................................................ 34
Spontane mutaties: herhalingen ................................................................................................................ 34
.................................................................................................................................................................. 35
Ziekte van Huntington ................................................................................................................................ 35
Geïnduceerde mutaties: chemisch ............................................................................................................... 35
Geïnduceerde mutaties: straling ................................................................................................................... 35
Xeroderma pigmentosum .......................................................................................................................... 35
Herstel thymine-dimeren (UV) ....................................................................................................................... 35
Base excisie herstel ................................................................................................................................... 35
Herstel foute basenparing ............................................................................................................................. 36
6) Populatiegenetica........................................................................................................................................ 37
Wat is populatiegenetica? ............................................................................................................................. 37
Hardy-Weinberg principe ........................................................................................................................... 37
Evolutie ......................................................................................................................................................... 37
niet-willekeurige paring.............................................................................................................................. 38
Genetische drift............................................................................................................................................. 38
Evolutietheorie: Darwin en Wallace, evolutie door natuurlijke selectie .......................................................... 39
Evolutie door natuurlijke selectie: fitness .................................................................................................. 39
Evolutie door sexuele selectie ................................................................................................................... 39
Evolutie in menselijke populaties............................................................................................................... 39
Behoud van variatie ....................................................................................................................................... 40
3
, Behoud van variatie: frequentie-afhankelijke selectie ................................................................................ 40
Behoud van variatie: variabele selectie ...................................................................................................... 40
Behoud van variatie: heterozygoot voordeel............................................................................................... 40
Selectie op continue variatie ......................................................................................................................... 40
Grenzen aan selectie ..................................................................................................................................... 41
Aanwijzingen voor evolutie ............................................................................................................................ 41
4
