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Attention! Test!

Human chromosomes Normal karyotype

Characterization of each chromosome

Classification of chromosomes

Pathologic karyotypes

Nomenclature of chromosomes

Methods of karyotyping (indications and limits)

Sex chromatin Sex chromosomes

X chromatin

Y chromatin

Barr body test (indications and limits)

F body test (indications and limits)

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

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INTERPHASE

G1

S

G2

Synthesis of RNA and proteins

2n = 2c

Chrs – single-chromatid

Sysnthesis of DNA and histones

Duplication of centriols

2n = 4c

Chrs – two-chromatids

Synthesis of tubulins and

mitogens

2n = 4c

Chrs – two-chromatids

MITOSIS

Prophase

Metaphase

Anaphase

Telophase

Condensation of chromosomes

Assembling of mitotic spindle,

nucleoli disappear

2n = 4c

Chromosomes in the middle of the

cell

2n = 4c

Longitudinal cleavage of

centromere

Chromatid disjunction

Simultaneous migration of

chromosomes 4n = 4c

Decondensation of chromatin,

cytokinesis

2n = 2c

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Mitosis represents an equationaldivision

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

Zygote

All cells are

identical;

resulted cells

will be also

identical

Biological importance of mitosis

Exact inheritance of information through generations

Growing of organism

Renewing of tissues

Regeneration of tissues

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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

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

Mutant clones – genetically differentcells of one organism

46

46

46

46

47

45

46

46

46

46

46

47

45

47

45

Zygote

Resulted cells

will divide and

will produce

an mosaic

Mosaic 46/47/45

Chromosomal mosaics may be:

Autosomal

Gonosomal

Mixed

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- 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 depends on:

Transversal cleavage of centromere:

Causes:- Mutations in centromere DNA

- Errors in assembling of kinetocore

- Errors in assembling of mitotic spindle

- Multi-polar centriole

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

Transversal cleavage of centromere:

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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,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-disjunction

causes:

- Errors of centromere of kinetocore proteins

- Mutations in centromere DNA

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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

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Anaphase lag

Consequences:mosaics which consist of normal cells2n=46 and cells with monosomy2n-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

Fecundation

Zigot(2n)

Mitosis, differentiation, growing

Mitosis, differentiation, growing

Copil(2n) Adulţi

(2n)

Meiosis

Spermatozoid (n)

Ovul (n)

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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 conţin 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

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Normal meiosis

A. Ovogenesis

46,XX

(2n = 46)

23,X

23,X

(1n = 2c)

23,X

23,X

23,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 meiosis

Maintaining of constant number of chromosomes

Genetic variability – intra- and inter-chromosomal recombination

Ensures inheritance

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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 monosomyand 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

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Chromosome non-disjunction during

Anaphase I

46,XX

24,XX

22

24,XX

24,XX

22

22

Disomic

gametes

Nullisomic

gametes

Disomic

Nullisomic

Chromosome non-disjunction during Anaphase I

Chromosome lag during Anaphase I

46,XX

23,X

22

23,X

23,X

22

22

Monosomic

gametes

Nullisomic

gametes

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Monosomic

Nullisomic

Chromosome lag during Anaphase I

Chromatid lag in Anaphase II

46,XX

23,X

23,X

23,X

23,X

23,X

22

Monosomic

gametes

Nullisomic

gamete

Chromatid lag in Anaphase II

Nullisomic

Mo

no

so

mic

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Chromatid non-disjunction during

Anaphase II

46,XX

23,X

23,X

23,X

23,X

24,XX

22

Monosomic

gametes

Nullisomic

gamete

Disomic

gamete

Chromatid non-disjunction during

Anaphase II

Nullisomic

Disomic

Mo

no

so

mic

Transversal cleavage of centromere

46,XX

23,X

23,X

23,X

23,X

23,iXp

Monosomic

23,iXq

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Transversal cleavage of cemtromere

mo

no

so

mic

2nd ovocytes non-disjunction

46,XX

23,X

23,X

23,X

23,X

46,XX

Monosomic

gametes

Diploid

gamete

Errors of fecundation

=>

Dispermy

Triploid

Diginy

Diandry

=>

=>

Egg Egg

Egg

Triploid

Triploid

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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)