Download VARIABILITY AND ITS FORMS Variability represents the organism`s

VARIABILITY AND ITS FORMS
Variability represents the organism’s propriety to obtain new characters (traits), different
from that of their parents. It means different genetic, biochemical, physiological or
morphological changes. Variability is e common propriety of organisms and ensures:
- Surviving of organisms in different environmental conditions
- Individual polymorphism
- Natural selection
- Evolution
- Appearance of different pathological states.
Different variations may be induced by internal factors (hormones, metabolites,
physiological states) and external factors (physical, chemical and biological). The most
important physical factors are radiations: UV (non-ionizing), X-rays, cosmic irradiations
(ionizing). The chemical substances, which may affect genetic material, are oxides, compounds
with chlorine, salts of heavy metals, vitamin C, and nitrates. The main biological factors are
viruses, bacterial and fungal toxins.
Classification of variability
There are two types of
variability: hereditary and nonhereditary.
Hereditary
variability can be due to
crossing over during meiosis
(recombination) or due to
mutations.
Non-hereditary
variability is also called
modification.
Nonhereditary (phenotypic)
variability
Each
phenotype
develops
under
specific
environmental
conditions.
Different factors (like sun
light, radiations, drugs) may
change the phenotype, without
modification of DNA. So, the
nonhereditary variations in phenotype don’t affect the genotype. The phenotypic
variations are also called modifications. Usually phenotypic modifications are
determined by genotype. Each character may vary in determined limits – this property is
called norm of reaction. [e.g. an white man exposed to sunlight (UV irradiation) became
more dark, but not a black]. Usually the modifications persist as long as the modification
factor acts. Modification’s characteristics:
- Represents nonhereditary variations of phenotype
- Represents adaptations to environmental conditions
- Are reversible (if they appear in adults)
- Different organisms present the same variations in identical conditions [in all people
UV light provoke darkness of the skin]
- The variation of phenotype is determined by organism’s genotype – norm of reaction
[in the same condition some people begin more dark, other – less].
Gene mutations
Some environment factors may have a destructive action on organism. In this case the
phenotype develops outside norm of reaction limits and an abnormal modification is produced.
The factors, which produce such abnormal modifications, are called teratogenes. The degree of
abnormality depends on the stage of development where it was produced: earlier damages are
more sever. Same times the phenotype closely resembles a genetic disease (state caused by
mutations), but has arisen by a completely different (environmentally determined) mechanism.
Such phenotype is called phenocopy.
Hereditary (genotypic) variability
The genotypic variability is determined by changes at the level of DNA. All genotypic
variations have the next proprieties:
- Are determined by changes in
genetic apparatus;
- Are induced by physical,
chemical
or
biological
conditions;
- May be inherited through
generations;
- Represent
the
basis
of
population polymorphism.
There are two types of
hereditary variations: mutational
and combinative.
Combinative variability
The recombination of genetic material takes place during sexual reproduction. There are
3 types of genetic recombination:
- Genomic recombination – random mating of gametes during fecundation.
- Inter-chromosomal recombination – random segregation of maternal and paternal
chromosomes during anaphase I. After meiosis may be 223 = 83886068 different
chromosome combinations in gametes.
- Intra-chromosomal recombination – represents the exchange of fragments between
homologous chromosomes during prophase I – crossing-over.
Mutational variability
Mutation is the process whereby changes occur in the quantity or structure of the genetic
material of an organism. Mutations are permanent alterations in the genetic material, which may
lead to changes in phenotype. An organism, gene, DNA sequence, etc. in which a mutation has
occurred is called a mutant.
Mutations can arise spontaneously as a result of events such as errors in the fidelity of
DNA replication or the movement of transposable genetic elements within genomes. They are
also induced following exposure to chemical or physical mutagens. Such mutation-inducing
agents include ionizing radiations, ultraviolet light and a diverse range of chemicals such as the
alkylating agents, and polycyclic aromatic hydrocarbons, all of which are capable of interacting
either directly or indirectly (generally following some metabolic biotransformations) with
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Gene mutations
nucleic acids. The DNA lesions induced by such environmental agents may lead to modifications
of the base sequence when the affected DNA is replicated or repaired and thus to a mutation.
Classification of mutations:
1) Depending on the cells in which mutations occur. Mutations may occur either in germ
cells or in somatic cells. Germ cell mutations can be transmitted to individuals of the next
generation and are usually found in all cells of the affected offspring. Somatic mutations are found
only in the descendents of the mutant cell, making the individual a "mosaic". Phenotypic
consequences are observable only if the mutations happen to interfere with the specific function of
the affected cells.
2) Depending on the origin of the mutation. Mutations can be spontaneous (which occur
naturally) and induced (they are produced when an organism is exposed to a mutagenic agent, or
mutagen; such mutations typically occur at much higher frequencies than spontaneous mutations
do).
3) Depending on the localization of a mutation in the cell. Mutations can be nuclear
(chromosome), in case the mutated gene is localized in a chromosome, or cytoplasmic, if the
mutated gene is localized in mitochondrial or chloroplast DNA.
4) Depending on the influence on viability of the organism. Mutations can be lethal (they cause
death of the embryo carrying the mutation), semi-lethal (they decrease drastically the viability of
the organism carrying the mutation), conditionally lethal (they may cause death of the organism
carrying the mutations in certain environment), neutral (they do not affect viability of the
individual), and enhancing (they increase viability of the individual).
5) Depending on the character of changes to the genetic material. In experimental genetics, the
following types of mutations can be distinguished:
Genome mutations involve alterations in the number of chromosomes. Whole sets of
chromosomes may be multiplied (polyploidy), or the number of copies of a particular chromosome
may be increased (trisomy) or decreased (monosomy).
Chromosome mutations. The structure of chromosome is changed, allowing microscopic
detection. The total number of chromosomes is not altered.
Gene mutations (point mutations). Here no changes of chromosomes can be detected
microscopically; the mutation can be inferred from a change in the phenotype be genetic analysis
or can be detected by DNA studies.
Gene (point) mutations
Gene mutations alter the hereditary material at the level of a gene. There are several types
of gene mutation: substitution, deletion, duplication, insertion, reversion, unequal crossing-over.
Substitution represents the replacing of one base with
another and may be two types: transition and transversion.
Transition mutations involve the substitution of one purine in the
DNA by another purine or one pyrimidine by another pyrimidine,
that is A by G and vice versa, or T by C and vice versa.
Transversions involve the replacement of a purine by a
pyrimidine and vice versa. Such base substitutions (also termed
base-pair substitutions or nucleotide substitutions) may affect the correct functioning of the
product of the modified gene; the extent of the effect can, however, range from the undetectable
to the severe. As the GENETIC CODE is degenerate, so that most of the amino acids inserted
into a growing polypeptide chain are coded for by more than one triplet, a base substitution may
simply convert one codon for a particular amino acid to another codon for the same amino acid
(samesens mutation). Even when the substitution results in the insertion of a different amino
acid into a polypeptide, a missense mutation, the amino acid may be an acceptable substitute
and thus not lead to any significant change in the activity of the polypeptide. However, some
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Gene mutations
missense amino-acid changes can have drastic effects upon the folding of polypeptide chains or
upon the configuration of the active site of an enzyme.
Other base substitutions may have drastic effects because
they convert a triplet coding for an amino acid into one of
the three termination signals, which lead to the premature
termination of polypeptide synthesis. Such nonsense
mutations are usually accompanied by the loss of function
of the gene product.
Frameshift mutations
The addition or deletion of base-pairs from the coding
sequence of a gene may lead to the production of frameshift
changes in the messenger RNA transcribed from that sequence
and a severe effect is nearly always produced in the resultant
polypeptide. Additions or deletions of one (or two or four) bases
cause a change in the reading frame of the mRNA which can
lead to premature termination as the result of generation of a stop
codon in the new reading frame, or to the insertion of a number
of incorrect amino acids in the growing polypeptide with a high
probability of producing a defective gene product.
In inversion a fragment of gene is rotated by 1800. As consequence a new sequence of
amino acids will be synthesized.
Reversion represents the change from a mutant phenotype to the original (wild type)
phenotype, which is usually due to back mutation. In intragenic suppression a phenotypic
correction of a frameshift mutation takes place when a compensating mutation within the same
gene restores the original reading frame.
Unequal crossing-over represents a nonreciprocal recombination event. This type of
recombination between arrays
of similar repeated sequences
may be responsible for the
expansion and contraction of
such arrays. [The hemoglobin
Lepore represents hemoglobin
product of the fusion gene that
results from unequal crossingover between b - and d -globin
genes.
The
intervening
material is deleted. The fusion
gene encodes a single b -like
chain that consists of the Nterminal sequence of d joined
to the C-terminal sequence of
b.
Several
types
of
hemoglobin Lepore are known, the difference between them lying in the point of transition from
d to b sequences. The phenotype is classified as d - b thalassaemia and in the homozygous state
there is a mild degree of anaemia].
Dynamic mutations
There are some mutations with an unusual pattern of inheritance, characteristic for a
group of genes, which give rise to a disease phenotype by dynamic mutation of a trinucleotide
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Gene mutations
repeat. As example may be used FMR1 gene, dynamic mutation in which is associated with
fragile X syndrome. This disease is characterized by mental retardation, elongated faces with
large ears, and macro-orchidism. The syndrome is unusual in that it is associated with the
appearance of a fragile site on the long arm of the X- chromosome. This can be visualized
cytogenetically in metaphase chromosomes prepared from lymphocytes of affected individuals.
Unusually for an X-linked recessive disorder, up to 30% of carrier females show some degree of
mental impairment, and the mutation may also be passed through males who do not show a
fragile X site (normal transmitting males). Additionally, there is an imbalance of penetrance of
the phenotype in the different generations of family members in which the mutation is
segregating. Nonpenetrant individuals are said to carry a premutation chromosome, that is, a
chromosome which has no abnormal phenotypic effect but which is capable of progressing to a
fully penetrant mutation on passage through a female oogenesis.
In normal gene there are up to 50 repeats of CGG trinucleotide. Expansions in FMR1 are
associated with fragile X
syndrome, but only when the
gene is methylated, and this
occurs when the number of CGG
repeats exceeds about 200 (full
mutation). Further expansion of
the repeat does not generate a
more severe phenotype. FMR1
has a premutation category,
with unmethylated expansion of
approximately 50-200 repeats.
Premutations have no phenotypic
effect, because the protein is
identical whether transcribed
from a normal or premutation
allele.
Although the mechanism
of amplification is unknown, it
most probably originates either as
an artefact of unscheduled DNA
replication or by unequal sister
chromatid
exchange
recombination.
The consequences of gene mutations
The primary effect of gene mutations is represented by modifications at the level of
amino acid sequence. The biological effect of such modifications depends on type of amino acids
involved in alteration and its position in polypeptide. A mutation may interfere the structure of
the rate of synthesis of a specific enzyme; as result a particular metabolic pathway will be
changed.
If a mutation affects the regulatory sequences, usually, only quantitative changes take
place. If the mutation changes the structural part of gene, may be both quantitative and
qualitative changes. As result the new alleles may be hypomorphic, hypermorphic, neomorphic
or amorphic (see “Gene interaction”).
Genetic load represents the average number of lethal alleles per individual within a given
population. A gene that has undergone a lethal mutation is typically incapable of producing an
active form of an indispensable protein. This is incompatible with survival in a haploid
organism. In a diploid organism lethal mutations are characterized as those that “kill” the
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Gene mutations
organism directly, usually early in development (embryonic lethal) or prevent it from
reproducing. Lethal mutations may be dominant or recessive.
Mutation rate. The number of mutation events in a particular unit of time, for example
the number of mutations per cell per generation, or the rate of mutation per locus per gamete. In
the study of heritable diseases, the mutation rate is expressed as mutations per locus per gamete,
which is effectively mutations per locus per generation (usually 1:25000 (or 4x10-5) – 1:1000000
(or 1x10-6). It can be measured directly in autosomal dominant diseases (as the number of cases
born to unaffected parents) and in diseases where carrier detection is possible. For autosomal
recessive diseases where carrier status cannot be ascertained, the mutation rate is measured
indirectly and involves estimates the effect of carrier status on fitness.
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Gene mutations
ANOMALIILE CROMOZOMICE
CHROMOSOMAL ABNORMALITIES
Chromosomal abnormalities represents chromosomes number modifications species
characteristic (46 in human somatic cells) or structural modifications of this. There are notions
of genomic mutations in literature ( that explains chromosomal number abnormalities), and
mutations or chromosomal aberrations (that explain chromosomal structure abnormalities).
Number chromosomal abnormalities affects whole the chromosome , and structural
abnormalities implicates rearrangements of chromosomes structure. Chromosomal abnormalities
possible causes:
mitosis deregulating factors that produce DNA tears or affects replication
chemical factors: cytostatines, antimethabolits, free radicals, alkilant agents
physical factors: ionizing radiations
biological factors: viruses
mother advanced age increase error risk in meiotic chromosomal segregation and
offspring’s aneuploidii risk
one of the parents is equilibrate congenital abnormality carrier (translocations,
inversions)
twins, more frequent in families with dizigot twins
chromosomal rearrangements (unequal crossing-over, recombination’s errors0
ovulation inductor therapy
Number abnormalities are clasificated in
Anomaliile cromozomice reprezintă modificări ale numărului cromozomilor caracteristic
speciei (46 în celulele somatice umane) sau modificări structurale ale acestora. În literatură sunt
întâlnite noţiunile de mutaţii genomice (ce explică anomaliile cromozomice de număr) şi mutaţii
sau aberaţii cromozomice (ce se referă la anomaliile de structură). Anomaliile cromozomice
numerice afectează întregul cromozom şi cele structurale implică rearanjamente ale structurii
cromozomilor (fig.9.4). Cauzele anomaliilor cromozomice ar putea fi:
factori care dereglează mitoza şi produc rupturi ale ADN-ului sau îi alterează replicarea:
factori chimici: citostatice, antimetaboliţi, radicali liberi, agenţii alkilanţi;
factori fizici: radiaţiile ionizante;
factori biologici: virusuri;
vârsta maternă avansată sporeşte riscul erorilor în segregarea cromozomilor în meioză şi a
aneuploiilor la descendenţi;
unul din părinţi este purtător de anomalie congenitală echilibrată (translocaţii, inversii);
gemelaritatea, mai frecvent în familiile gemenilor dizigoţi;
rearanjările intercromozomice (crossing-over inegal, erori de recombinare);
terapia cu inductori de ovulaţie.
Anomaliile numerice sunt clasificate în: poliploidii (prezenţa în plus a unor seturi
haploide de cromozomi) şi aneuploidii (prezenţa în plus sau absenţa unui cromozom întreg).
Poliploidiile, în dependenţă de numătul de seturi haploide prezente în nucleul celulei
somatice, pot fi: triploidii (3n) - 69,XXX sau 69,XXY sau 69,XYY; tetraploidii (4n )- 92,XXXX
sau 92,XXYY; etc.
Triploidia (3n) poate rezulta prin fecundarea de către un gamet normal (n = haploid) a unui
gamet anormal (2n=diploid); gametul diploid este rezultatul neseparării citelor de ordinul II în
meioza parentală (de obicei, în cursul ovogenezei, neexpulzarea primului globul polar - diginie;
uneori în cursul spermatogenezei - diandrie); prin erori în cursul fecundării: fecundarea unui ovul
(n) de către 2 spermatozoizi (2n) – dispermie.
Tetraploidia (4n) poate fi rezultatul unei erori de clivaj în cursul primei diviziuni mitotice a
zigotului şi dublarea numărului de cromozomi imediat după fecundare (endomitoză) sau prin
fecundarea a 2 gameţi diploizi (2n+2n=4n). Poliploidiile interesează o mare cantitate de material
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Gene mutations
genetic şi la om sunt, de regulă, neviabile (manifestându-se prin avort în trimestrul I de sarcină sau
nou-născuţi morţi).
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Fig. 9.4. Clasificarea anomaliilor cromozomice
Aneuploidile se caracterizează prin prezenţa în plus faţă de numărul diploid normal
sau absenţa a 1-2-3 cromozomi. Majoritatea aneuploidiilor sunt consecinţa unor erori de segregare
cromozomică sau cromatidiană în cursul diviziunii celulare, numite nedisjuncţii. În cazul
nedisjuncţiilor numărul de cromozomi din celulele fiice nu este egal. Aceste anomalii se pot
produce în meioza I, meioza II sau în mitoză. Rareori, gameţii nulisomici, iar apoi embrionii
monosomici, pot rezulta datorită pierderii cromozomilor printr-o întârziere anafazică la nivelul
plăcii ecuatoriale. Aneuploidiile omogene sunt rezultatul fecundării unui gamet normal de către un
gamet aneuploid produs prin erori de distribuţie a materialului genetic în cursul meiozei parentale.
Aneuploidiile în mozaic sunt rezultatul erorilor de distribuţie a materialului genetic în cursul mitozei
(de obicei, diviziunile de segmentare ale primelor stadii embrionare).
Clasificarea aneuploidiilor:
a) după surplus sau lipsă de cromozomi:
monosomie (2n-1) - absenţa unui cromozom;
trisomie (2n+1) - prezenţa unui cromozom supranumerar;
b) după tipul cromozomului implicat:
aneuploidii autozomale
aneuploidii gonozomale
c) după numărul de celule afectate:
anomalii omogene (prezenţa anomaliei în toate celulele organismului);
anomalii în mozaic (prezenţa unor linii celulare anormale şi normale în acelaşi organism);
d) după asocierea sau lipsa acesteia cu anomaliile de structură:
anomalii libere – fără anomalii cromozomice structurale;
anomalii prin translocaţie – prezenţa în plus a unor cromozomi ataşaţi la alţii fără
modificarea numărului diploid normal, sau falsa absenţă a unui cromozom ca urmare a fuzionării cu
un altul. Uneori termenul se foloseşte referitor la orice modificare cantitativă a materialului genetic,
inclusiv la anomaliile congenitale structurale): load
anomalii complete – prezenţa în plus sau lipsa unui cromozom în întregime;
anomalii parţiale – prezenţa în plus sau lipsa unui segment cromozomic.
Efectele şi gravitatea anomaliilor cromozomice cantitative depind de:
tipul de anomalie şi mărimea dezechilibrului genetic - cu cât defectul cantitativ este mai
mare, cu atât consecinţele sunt mai grave; deficitul are consecinţe mai grave decât excesul;
conţinutul genic şi activitatea cromozomului implicat – de ex., trisomia 1 nu este viabilă,
trisomia 21 - da.
tipul şi numărul de celule afectate - afectarea celulelor somatice duce la modificarea
fenotipului individului; afectarea celulelor sexuale duce la apariţia tulburărilor de reproducere.
Monosomiile sunt mai grave decât trisomiile. Singura monosomie viabilă la specia
umană este monosomia X; monosomiile autosomale, Y şi 98% din zigoţii cu monosomie X se
elimină ca produşi de avort, în trimestrul I de sarcină.
Trisomiile cromozomilor mari, activi genetic, sunt neviabile, producînd avort în
trimestrul I de sarcină sau nou-născuţi morţi. Viabile pot fi trisomiile 8, 13, 18, 21, fiind
responsabile de multiple anomalii de dezvoltare (sindroame):
sindromul trisomiei 8 - 47, XX (XY), +8;
sindromul Patau - 47, XX (XY), +13;
sindromul Edwards - 47, XX (XY), +18;
sindromul Down - 47, XX (XY), +21.
Anomaliile cromozomice viabile (sindroamele cromozomice) prezintă modificări
fenotipice comune (tulburări de creştere pre- şi postnatală; întârziere în dezvoltarea psiho-motorie şi
debilitate mintală; multiple anomalii viscerale, disgenezii gonadice) şi modificări specifice ale
cromozomului sau cromozomilor implicaţi.
ANOMALIILE CROMOZOMICE DE STRUCTURĂ
Gene mutations
Anomaliile cromozomice structurale pot fi clasificate în funcţie de efectul fenotipic şi de
mecanismul de producere. Pe baza efectului fenotipic, anomaliile cromozomice structurale se
împart în: echilibrate (inversiile şi translocaţiile), care nu modifică fenotipul purtătorului şi
neechilibrate (deleţiile, duplicaţiile, etc.), care produc fenotipuri anormale. În raport cu
mecanismul de producere, anomaliile cromozomice structurale pot fi grupate în: anomalii
produse printr-o singură ruptură cromozomică (deleţia terminală), anomalii produse prin două
rupturi cromozomice în acelaşi cromozom (deleţiile interstiţiale, inversiile, cromozomii inelari),
anomalii produse prin rupturi în cromozomi diferiţi (cromozomii dicentrici, translocaţiile
reciproce şi cele robertsoniene; inserţiile).
Anomalii echilibrate
Inversia reprezintă o anomalie de structură, caracterizată prin modificarea ordinii genelor de
pe un fragment cromozomic. Mecanismul de producere constă în ruperea unui cromozom în două
puncte şi rotirea cu 180° a fragmentului intermediar.
Inversiile pot fi de două tipuri: pericentrice: produse prin ruptura unui cromozom în două
puncte situate pe braţe diferite, urmată de rotaţia cu 180o a fragmentului intermediar şi reunirea
fragmentelor; în urma acestei rotaţii se poate produce modificarea configuraţiei cromozomului;
paracentrice: produse prin ruptura unui cromozom în două puncte situate pe acelaşi braţ, urmată de
rotaţia cu 1800 a fragmentului intermediar şi reunirea fragmentelor; în urma acestei rotaţii nu se
modifică configuraţia cromozomului, ci numai ordinea benzilor.
Translocaţiile sunt anomalii de structură caracterizate prin trecerea unuia sau mai multor
fragmente cromozomice de pe un cromozom pe altul, fără a determina modificări fenotipice.
Translocaţiile pot fi de trei tipuri:
reciproce - produse prin ruperea a doi cromozomi în câte un punct, urmată de schimbul
fragmentelor rupte şi realipirea cromozomilor;
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Gene mutations
cu inserţii - produse prin ruperea a doi cromozomi neomologi, unul într-un punct şi celălalt
în două puncte de pe acelaşi braţ, urmată de inserarea în punctul de ruptură al primului cromozom
al fragmentului intermediar din al doilea cromozom;
robertsoniene - produse prin ruperea a doi cromozomi acrocentrici la nivelul centromerului
urmată de fuziunea braţelor lungi (fuziune centrică) şi pierderea braţelor scurte (conţin doar gene
pentru ARN ribosomal şi, astfel, pierderea lor nu determină modificări fenotipice); acest tip de
anomalii conduce la scăderea numărului de cromozomi de la 46 la 45.
Anomaliile cromozomice echilibrate nu modifică fenotipul individului, deoarece reprezintă
rearanjări cromozomice, care nu determină modificări cantitative ale materialului genetic. Dar,
purtătorul unei translocaţii echilibrate, deşi normal fenotipic, poate produce gameţi anormali
datorită erorilor de conjugare şi erorilor de segregare (nedisjuncţii) ale cromozomilor implicaţi în
translocaţie (fig. 9.5).
Anomalii neechilibrate
Deleţiile sunt anomalii structurale caracterizate prin pierderea unor fragmente cromozomice.
Anomaliile pot fi de două tipuri:
terminale - produse prin ruperea unui cromozom într-un punct, urmată de pierderea
fragmentului terminal;
interstiţiale - produse prin ruperea unui cromozom în două puncte situate pe acelaşi braţ,
urmată de pierderea fragmentului intermediar.
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Gene mutations
Deleţiile se pot produce
şi prin alte mecanisme: crossing-
over inegal între cromozomi
omologi
aliniaţi
eronat,
segregarea
cromozomilor
anormali în cursul meiozei
parentale în cazul în care unul
din părinţi prezintă o anomalie
echilibrată. Deleţia are ca efect
apariţia unei diferenţe de
lungime
între
cromozomii
omologi.
Fig. 9.5. Consecinţele translocaţiei robertsoniene t(13q21q) asupra
gametogenezei
Duplicaţiile
sunt
anomalii structurale caracterizate
prin prezenţa în dublu exemplar
a unui fragment cromozomic.
Anomalia se poate produce prin
crossing-over inegal şi segregare
anormală a cromozomilor cu translocaţie.
Cromozomii inelari apar prin ruperea unui cromozom în două puncte situate pe braţe
diferite, urmată de pierderea segmentelor terminale (acentrice) şi reunirea capetelor segmentului
centric într-o structură inelară.
Izocromozomii sunt cromozomi anormali formaţi fie numai din braţe scurte, fie numai din
braţe lungi. Mecanismul de apariţie a anomaliei constă în clivarea transversală a centromerului.
Anomalia are ca efect apariţia unui cromozom care prezintă concomitent deleţia unuia din
braţe şi duplicaţia celuilalt braţ.
Cromozomii dicentrici sunt cromozomi anormali caracterizaţi prin prezenţa în acelaşi
cromozom a doi centromeri. Mecanismul de producere constă în ruperea a doi cromozomi în câte
un punct, urmată de pierderea fragmentelor terminale şi unirea celor două segmente cromozomice,
care prezintă centromere, într-un singur cromozom.
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Gene mutations
Anomaliile cromozomice neechilibrate determină un dezechilibru cantitativ al materialului
genetic (în plus sau în minus) ce se manifestă fenotipic asemănător anomaliilor numerice (trisomii
parţiale sau monosomii parţiale). Trisomiile şi monosomiile parţiale ale unui cromozom determină
multiple caractere anormale în "tip şi contratip" asemănătoare cu monosomiile şi trisomiile totale
ale aceluiaşi cromozom: trisomia 18 (sdr. Edwards) şi monosomia parţială determinată de 18q-;
trisomia 13 (sdr. Patau) şi monosomia parţială determinată de r(13).
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