inheritance of genetic information errors of mitosis...
TRANSCRIPT
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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)