INHERITANCE OF INHERITANCE OF GENETIC GENETIC INFORMATIONINFORMATION

ERRORS OF MITOSIS ERRORS OF MITOSIS AND MEIOSISAND MEIOSIS

INHERITANCE OF GENETIC INHERITANCE OF GENETIC INFORMATION IS DONE VIA INFORMATION IS DONE VIA CHROMOSOMESCHROMOSOMES

FROM SOMATIC CELL TO SOMATIC CELL Replication of DNA Segregation of genetic material in metaphase

(equational division)

FROM PARENTS TO OFFSPRING Gametogenesis Fecundation

INTERPHASEINTERPHASE

G1

S

G2

Synthesis of RNA and proteins 2n = 2c Chrs – single-chromatidSysnthesis of DNA and histonesDuplication of centriols 2n = 4cChrs – two-chromatids

Synthesis of tubulins and mitogens

2n = 4cChrs – two-chromatids

MITOSISMITOSIS

Prophase

Metaphase

Anaphase

Telophase

Condensation of chromosomesAssembling of mitotic spindle, nucleoli disappear 2n = 4cChromosomes in the middle of the cell 2n = 4c

Longitudinal cleavage of centromereChromatid disjunctionSimultaneous migration of chromosomes 4n = 4c

Decondensation of chromatin, cytokinesis 2n = 2c

Mitosis represents an equational Mitosis represents an equational division because from a diploid division because from a diploid cell cell (2n=46) (2n=46) will be produced two will be produced two diploid cellsdiploid cells (2n=46) (2n=46)

All diploid cells (somatic) contain identical information, the same numbers of chromosomes.

Clone – group of cells resulted from a single cell by mitotic divisions

46

46

46

46

46

46

46

46

46

46

46

46

46

46

46

ZygoteZygote

All cells are identical;

resulted cells will be also identical

Biological importance of Biological importance of mitosismitosis Exact inheritance of information through

generations Growing of organism Renewing of tissues Regeneration of tissues

STEPS OF INHERITANCE OF STEPS OF INHERITANCE OF GENETIC INFORMATION FROM GENETIC INFORMATION FROM CELL TO CELLCELL TO CELL::

I STEP – DNA replication during S phase of interphase

II STEP – equal distribution of genetic

information in daughter cells during anaphase

Errors of distribution of Errors of distribution of genetic material during genetic material during mitosismitosis A. Errors of DNA replication or repair

which lead to:

- Gene mutations in somatic cells

- Mutant clones which may be inherited by different somatic cells

Transversal cleavage of centromere

- Chromatid non-disjunction

- Anaphase lag

- If resulted cells are viable, they will produce clones of mutant cells; resulted organism is called mosaic – it contains different cell lines.

B. B. Errors of distribution of genetic Errors of distribution of genetic material during anaphase as result ofmaterial during anaphase as result of::

Mutant clonesMutant clones – – genetically genetically different cells of one different cells of one organismorganism

46

46

46

46

47

45

46

46

46

46

46

47

45

47

45

ZygoteZygote

Resulted cells will divide and will produce an mosaic

Mosaic Mosaic 4646//4747//4545

Chromosomal mosaics may beChromosomal mosaics may be::

Autosomal Gonosomal Mixed

- Ontogenetic stage- During embryogenesis

- Congenital abnormalities- Postnatal

- Cancers

- Involved chromosome- Chromosome with more (stronger) or less genes- Gonosome or autosome (stronger)

- Tipul anomaliei- Monosomii (mai grav) sau trisomii- Complete (mai grav) sau parţiale

Consequences of mosaics in phenotype Consequences of mosaics in phenotype depends ondepends on::

Transversal cleavage of Transversal cleavage of centromerecentromere::

Causes: - Mutations in centromere DNA- Errors in assembling of kinetocore- Errors in assembling of mitotic spindle- Multi-polar centriole

ConsequencesConsequences::- Isochromosome p (ip) – duplications of genes

in p arm and absence of genes in q- Isochromosome q (iq) – duplications of genes

in q arm and absence of genes in p- Mosaic: 46,ip/46,iq or 46/46,ip/46,iq

- ExamplesExamples::- 46,X,i(Xp) or 46,X,i(Xq) – Turner phenotype

Transversal cleavage of Transversal cleavage of centromerecentromere::

Longitudinal cleavage of centromere

Transversal cleavage of centromere; formation ofiso p and iso q

46,XY 46,X,i(Yp) and 46,X,i(Yq)

Transversal cleavage of Transversal cleavage of centromerecentromere

46,XX 46,X,i(Xp)

46,XX 46,X,i(Xp)

46,XX 46,X,i(Xp)

46,XX 46,XX

46,X,i(Xp) 46,X,i(Xq)

46,XX 46,X,i(Xq)

46,X,i(Xq) 46,X,i(Xq)

Mosaic: 46,XX/46,X,i(Xp)/46,X,(iXq) Mosaic: 46,X,i(Xp)/46,X,i(Xq)

Turner phenotype Turner phenotype

Chromatid non-disjunctionChromatid non-disjunction

causes:- Errors of centromere of kinetocore proteins- Mutations in centromere DNA

Chromatid non-disjunctionChromatid non-disjunction

Consequences:- Abnormal cells with:Trisomy (2n+1=47 chrs) and Monosomy (2n-1=45 chrs)

Mosaics: 46/47/45; 47/45; 46/47

Examples: 46,XX/47,XX,+21 – Down syndrome 46,XY/47,XY,+13 – Patau syndrome 46,XX/47,XXX/45,X 46,XY/47,XXY - Klinefelter syndrome

Chromatid disjunction Chromatid non-disjunction

Trisomy

Monosomy

Anaphase lagAnaphase lag

Causes:- Different viscosity of cytoplasm- Errors in assembling of tubulines- Mutagens

Anaphase lagAnaphase lagConsequences: mosaics which consist of normal cells

2n=46 and cells with monosomy 2n-1=45

Mosaic: 46/45

Examples: 46,XX/45,X – Turner sdr.

Simultaneous migration of chromatids

Anaphase lag

Monosomy

Inheritance of genetic material from generation to Inheritance of genetic material from generation to generationgeneration

Fecundation

Zigot(2n)

Mitosis, differentiation, growing

Mitosis, differentiation, growing

Copil(2n) Adulţi

(2n)

Meiosis

Spermatozoid (n)

Ovul (n)

Steps of inheritance of genetic Steps of inheritance of genetic material from parents to material from parents to offspringoffspring:: I – Gametogenesis – formation of gametes in gonads:

- Mature gametes – eggs and sperms contain haploid sets of chromosomes (n=23 chrs)

- Celule ce conţin material genetic recombinat

II – Fecundation – fertilization and formation of zygote:- Diploid cell 2n=46 chrs- During fertilization genomic recombination take place

GametogenesisGametogenesis::I – multiplication of gametogonia (mitosis)

II – growing of 1st gametocites

III – maturation of gametes (meiosis)

IV – differentiation of sperms

Normal meiosisNormal meiosis

A. Ovogenesis

46,XX(2n = 46)

23,X

23,X(1n = 2c)

23,X

23,X23,X

23,X

(1n = 1c)

(1n = 1c)

B. Spermatogenesis

46,XY(2n= 4c)

23,X

23,Y

(1n = 2c)

23,X

23,X 23,Y

23,Y

(1n = 1c)

(1n = 1c)

Monosomic gametes

Biologic importance of Biologic importance of meiosismeiosis

Maintaining of constant number of chromosomes

Genetic variability – intra- and inter-chromosomal recombination

Ensures inheritance

Types of errors during Types of errors during meiosismeiosis

A. A. Errors of recombinationErrors of recombination:: - - unequal crossing-overunequal crossing-over chrs with chrs with

deletion and chrs with duplicationdeletion and chrs with duplication

Types of errors during Types of errors during meiosismeiosis

B. B. Errors of distributionErrors of distribution:: Chromatid non-disjunction in anaphase Chromatid non-disjunction in anaphase

II gametes with disomy and gametes with disomy and nullisomynullisomy

Chromatid non-disjunction in anaphase Chromatid non-disjunction in anaphase IIII gametes with monosomy, disomy gametes with monosomy, disomy and nullisomy and nullisomy

Anaphase I and II lagAnaphase I and II lag gametes with gametes with monosomy and nullisomymonosomy and nullisomy

Transversal cleavage of centromere in Transversal cleavage of centromere in Anaphase II Anaphase II

gametes with chrsgametes with chrs i(p) i(p) and chrs and chrs i(q)i(q) Non-disjunction of 2Non-disjunction of 2ndnd ovocytes ovocytes

diploid eggsdiploid eggs

Errors during meiosisErrors during meiosis

CausesCauses::

1.1. Aged mother Aged mother:: Unequal crossing-overUnequal crossing-over Errors in mitotic spindleErrors in mitotic spindle

2. 2. Carriers of ballanced chromosomal Carriers of ballanced chromosomal aberrations aberrations ( (inv, t, robinv, t, rob))

3. 3. Mutagenes Mutagenes

Chromosome non-disjunction Chromosome non-disjunction during Anaphase Iduring Anaphase I

46,XX46,XX

24,XX24,XX

2222

24,XX24,XX

24,XX24,XX

2222

2222

Disomic Disomic gametesgametes

Nullisomic Nullisomic gametesgametes

DisomicDisomic

NullisomicNullisomic

Chromosome non-disjunction during Chromosome non-disjunction during Anaphase IAnaphase I

Chromosome lag during Chromosome lag during Anaphase IAnaphase I

46,XX46,XX

23,X23,X

2222

23,X23,X

23,X23,X

2222

2222

Monosomic Monosomic gametesgametes

Nullisomic Nullisomic gametesgametes

MonosomicMonosomic

NullisomicNullisomic

Chromosome lag during Anaphase IChromosome lag during Anaphase I

Chromatid lag in Anaphase IIChromatid lag in Anaphase II

46,XX46,XX

23,X23,X

23,X23,X

23,X23,X

23,X23,X

23,X23,X

2222

Monosomic Monosomic gametesgametes

Nullisomic Nullisomic gametegamete

Chromatid lag in Anaphase Chromatid lag in Anaphase IIII

NullisomicNullisomic

Mo

no

som

icM

on

oso

mic

Chromatid non-disjunction Chromatid non-disjunction during Anaphase IIduring Anaphase II

46,XX46,XX

23,X23,X

23,X23,X

23,X23,X

23,X23,X

24,XX24,XX

2222

Monosomic Monosomic gametesgametes

Nullisomic Nullisomic gametegamete

Disomic Disomic gametegamete

Chromatid non-disjunction Chromatid non-disjunction during Anaphase IIduring Anaphase II

NullisomicNullisomic

DisomicDisomic

Mo

no

som

icM

on

oso

mic

Transversal cleavage of Transversal cleavage of centromerecentromere

46,XX46,XX

23,X23,X

23,X23,X

23,X23,X

23,X23,X

23,iXp23,iXp

MonosomicMonosomic

23,iXq23,iXq

Transversal cleavage of Transversal cleavage of cemtromerecemtromere m

on

oso

mic

mo

no

som

ic

22ndnd ovocytes non-disjunction ovocytes non-disjunction

46,XX46,XX

23,X23,X

23,X23,X

23,X23,X

23,X23,X

46,XX46,XX

Monosomic Monosomic gametesgametes

Diploid Diploid gametegamete

Errors of fecundationErrors of fecundation

=>

DispermyDispermy

TriploidTriploid

DiginyDiginy

DiandryDiandry

=>

=>

EggEgg EggEgg

EggEgg

TriploidTriploid

TriploidTriploid

As result of errors during meiosis will be produced abnormal gametes (genetically unbalanced) which, after fertilization with normal gametes, will produce abnormal zygotes (monosomy, trisomy, triploid)