INHERITANCE OF GENETIC INFORMATION ERRORS OF MITOSIS AND MEIOSIS

INHERITANCE OF GENETIC INFORMATION IS DONE VIA CHROMOSOMES

FROM SOMATIC CELL TO SOMATIC CELL

Replication of DNA Segregation of genetic material in metaphase (equational division)

FROM PARENTS TO OFFSPRING

Gametogenesis Fecundation

Synthesis of RNA and proteins

2n = 2c G1 Chrs single-chromatid Sysnthesis of DNA and histones

Duplication of centriols

INTERPHASE

2n = 4c Chrs two-chromatids

Synthesis of tubulins and mitogens

G2

2n = 4c Chrs two-chromatids

Prophase

Condensation of chromosomes Assembling of mitotic spindle, nucleoli disappear 2n = 4c

Chromosomes in the middle of the Metaphase cell 2n = 4c

MITOSIS
Anaphase

Longitudinal cleavage of centromere Chromatid disjunction Simultaneous migration of chromosomes 4n = 4c

Decondensation of chromatin, Telophase cytokinesis 2n = 2c

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

All cells are identical; resulted cells will be also identical

Zygote

Biological importance of mitosis

Exact inheritance of information through generations Growing of organism Renewing of tissues Regeneration of tissues

STEPS OF INHERITANCE OF GENETIC INFORMATION FROM CELL 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 genetic material during mitosis

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

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

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.

Mutant clones genetically different cells of one organism

46 46 46 47 46 46 47 45 46 46 47 45

46
46

45

Resulted cells will divide and will produce an mosaic

Zygote

Mosaic 46/47/45

Chromosomal mosaics may be:

Autosomal Gonosomal Mixed

Consequences of mosaics in phenotype depends on:

-

Ontogenetic stage
-

During embryogenesis
-

Congenital abnormalities Cancers

Postnatal
-

Involved chromosome
-

Chromosome with more (stronger) or less genes Gonosome or autosome (stronger) Monosomii (mai grav) sau trisomii Complete (mai grav) sau pariale

Tipul anomaliei
-

Transversal cleavage of centromere:

Causes:

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

Transversal cleavage of centromere:

Consequences:
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 Examples: 46,X,i(Xp) or 46,X,i(Xq) Turner phenotype
-

Longitudinal cleavage of centromere

Transversal cleavage of centromere; formation of iso p and iso q

46,XY

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

Transversal cleavage of centromere

46,XX 46,XX 46,XX 46,X,i(Xp) 46,X,i(Xp) 46,X,i(Xp)

46,XX
46,X,i(Xp) 46,XX 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-disjunction
-

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

Chromatid 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 lag
-

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

Anaphase lag
Consequences: 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 generation

Mitosis, differentiation, growing Mitosis, differentiation, growing

Copil (2n)

Aduli (2n)

Zigot (2n)

Meiosis

Spermatozoid (n)

Fecundation

Ovul (n)

Steps of inheritance of genetic material from parents to offspring:

-

I Gametogenesis formation of gametes in gonads: Mature gametes eggs and sperms contain haploid sets of chromosomes (n=23 chrs) Celule ce conin material genetic recombinat II Fecundation fertilization and formation of zygote: Diploid cell 2n=46 chrs During fertilization genomic recombination take place

Gametogenesis:
I multiplication of gametogonia (mitosis)
II growing of 1st gametocites III maturation of gametes (meiosis) IV differentiation of sperms

Normal meiosis
A. Ovogenesis 46,XX (2n = 46) 23,X

23,X (1n = 2c) 23,X

(1n = 1c)

23,X 23,X

B. Spermatogenesis 46,XY (2n= 4c) 23,X (1n = 2c) 23,Y

(1n = 1c) 23,X Monosomic gametes

23,X (1n = 1c) 23,X 23,Y (1n = 1c) 23,Y

Biologic importance of meiosis

Maintaining of constant number of chromosomes Genetic variability intra- and interchromosomal recombination Ensures inheritance

Types of errors during meiosis

A. Errors of recombination:

- unequal crossing-over chrs with deletion and chrs with duplication

Types of errors during meiosis

B. Errors of distribution:

Chromatid non-disjunction in anaphase I gametes with disomy and nullisomy Chromatid non-disjunction in anaphase II gametes with monosomy, disomy and nullisomy Anaphase I and II lag gametes with monosomy and nullisomy Transversal cleavage of centromere in Anaphase II gametes with chrs i(p) and chrs i(q) Non-disjunction of 2nd ovocytes diploid eggs

Errors during meiosis

Causes: 1. Aged mother: Unequal crossing-over Errors in mitotic spindle 2. Carriers of ballanced chromosomal aberrations (inv, t, rob) 3. Mutagenes

Chromosome non-disjunction during Anaphase I

24,XX

24,XX
24,XX 46,XX 22 22 22

Disomic gametes
Nullisomic gametes

Chromosome non-disjunction during Anaphase I

Disomic

Nullisomic

Chromosome lag during Anaphase I

23,X

23,X
23,X 46,XX 22 22 22

Monosomic gametes
Nullisomic gametes

Chromosome lag during Anaphase I

Monosomic

Nullisomic

Chromatid lag in Anaphase II

23,X

23,X
23,X 46,XX 23,X 23,X 22

Monosomic gametes

Nullisomic gamete

Chromatid lag in Anaphase II

Monosomic Nullisomic

Chromatid non-disjunction during Anaphase II

23,X

23,X
23,X 46,XX 24,XX 23,X 22

Monosomic gametes
Disomic gamete Nullisomic gamete

Chromatid non-disjunction during Anaphase II

Monosomic Disomic Nullisomic

Transversal cleavage of centromere

23,X 23,X
23,X 46,XX 23,iXp 23,X 23,iXq

Monosomic

Transversal cleavage of cemtromere

monosomic

2nd ovocytes non-disjunction

23,X

23,X
23,X 46,XX 23,X 46,XX

Monosomic gametes
Diploid gamete

Errors of fecundation
Dispermy Diandry

=>
Egg

=> Egg
Triploid

Triploid

Diginy => Egg Triploid

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)