Medical Genetics
10 人类染色体畸变
chromosome aberration
Medical Genetics
Any type of change in the
chromosome structure or number
(deficiencies,duplications,
translocations,inversions,etc.),
Medical Genetics
Although it can be a mechanism
for enhancing genetic diversity,such
alterations are usually fatal or ill-
adaptive,especially in animals,
Medical Genetics
1,factors inducing chromosome aberration
A,Ionizing radiation
Ionizing radiation produces
rearrangements of the genome,
Medical Genetics
Medical Genetics
When irradiation occurs during
the G0/G1 phase of the cell cycle,
large-scale rearrangements appear
as exchange-type chromosome
aberrations at the next mitosis,Such
aberrations can alter cellular
phenotypes,and are important in
various areas of biology,
Medical Genetics
Medical and public-health
applications include perinatal
diagnostics characterization of specific
cancer types,carcinogenesis risk
estimation,radiation biodosimetry and
radiotherapeutic treatment planning,
Medical Genetics
Analyzing chromosome aberrations
helps characterize repair/misrepair
pathways involved in the processing of
DNA damage,Ionizing radiation has some
unique features as a probe of such
pathways,Compared to other genotoxic
agents,it produces copious quantities of
DNA double strand breaks (DSBs),and its
timing can be controlled more accurately,
Medical Genetics
Moreover,initial radiation
damage has a discrete,stochastic
character that can be modulated by
using different kinds of radiation (e.g,
a -particles versus x-rays) having
different ionization densities,
Medical Genetics
The spectrum of different
radiation-induced chromosome
aberrations is informative about the
geometry of chromosomes during
interphase,and vice versa,
Medical Genetics
Chromosomal instability,in which
new aberrations (though often not of
the type characteristic of G0/G1
damage) continue to arise many
generations after irradiation,
represents a form of genomic
instability,and genomic instability is
prominent during neoplastic
progression,
Medical Genetics
B,chemical mutagen
A kind of substances,such as
drugs or toxins,that causes
chromosomal aberrations of living
organisms,or increase the rate of
mutation,
Medical Genetics
2,chromosomal aberrations
A,chromosome numerical
aberration
Numerical aberration is a change
in the number of chromosomes from
the normal number characteristic of
the human beings,
Medical Genetics
(1) Euploidy is the condition of
having a normal number of
structurally normal
chromosomes,
Euploid human females have 46
chromosomes (44 autosomes and
two X chromosomes),
Medical Genetics
Polyploidy is a multiple of the
haploid chromosome number (n)
other than the diploid number (i.e.,
3n,4n and so on),
Medical Genetics
(2) Aneuploidy is the condition of
having less than or more than the
normal diploid number of
chromosomes,and is the most
frequently observed type of
cytogenetic abnormality,
In other words,it is any deviation from
euploidy,although many authors restrict
use of this term to conditions in which
only a small number of chromosomes are
missing or added,
Medical Genetics
Generally,aneuploidy is recognized
as a small deviation from euploidy for
the simple reason that major
deviations are rarely compatible with
survival,and such individuals usually
die prenatally,
Medical Genetics
The two most commonly
observed forms of aneuploidy are
monosomy and trisomy,
Medical Genetics
Monosomy is lack of one of a pair
of chromosomes,An individual having
only one chromosome 6 is said to have
monosomy 6,A common monosomy seen
in many species is X chromosome
monosomy,also known as Turner's
syndrome,Monosomy is most commonly
lethal during prenatal development,
Medical Genetics
Trisomy is having three
chromosomes of a particular type,A
common autosomal trisomy in humans in
Down syndrome,or trisomy 21,in which a
person has three instead of the normal
two chromosome 21s,Trisomy is a specific
instance of polysomy,a more general
term that indicates having more than two
of any given chromosome,
Medical Genetics
Another type of aneuploidy is
triploidy,A triploid individual has
three of every chromosome,that is,
three haploid sets of chromosomes,
A triploid human would have 69
chromosomes (3 haploid sets of 23),
Medical Genetics
Production of triploids seems to
be relatively common and can occur
by,for example,fertilization by two
sperm,
Medical Genetics
However,birth of a live triploid is
extraordinarily rare and such
individuals are quite abnormal,The
rare triploid that survives for more
than a few hours after birth is almost
certainly a mosaic,having a large
proportion of diploid cells,
Medical Genetics
(3) Chromosome non-disjunction
The failure of a pair of homologous
chromosomes to separate properly during
meiosis,The failure of homologues (at
meiosis) or sister chromatids (at mitosis)
to separate properly to opposite poles,
that is two chromosomes or chromatids go
to one pole and none to the other,
Medical Genetics
Non-disjunction can occur during
meiosis I or meiosis II,An error in
the proper segregation of the
chromosomes during both meiosis I
and II are pictured below,
Medical Genetics
In meiosis I,the error occurs
when the homologous pairs both
travel into the same daughter
cell,The result is two daughter cells
that have two copies of the
chromosome (called disomic cells)
and two cells that are missing that
chromosome (called nullisomic
cells),
Medical Genetics
Non-disjunction in Meiosis I,
Medical Genetics
In meiosis II,the error occurs
when the sister chromatids will not
separate and thus travel into the
same daughter cell,
Medical Genetics
Non-disjunction in Meiosis II,
Medical Genetics
Fertilization following Meiosis I error,
Medical Genetics
Fertilization following Meiosis II error,
Medical Genetics
Medical Genetics
B,Chromosome Structural
Aberration
Structural aberration is a change
in chromosome structure detectable
by microscopic examination of the
metaphase stage of cell division,
observed as deletions and fragments,
intrachanges or interchanges,
Medical Genetics
(1) A chromosome deletion occurs
when the chromosome breaks
and a piece is lost,This of course
involves loss of genetic information
and results in what could be
considered "partial monosomy" for
that chromosome,
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
(2) A related abnormality is a
chromosome inversion,
In this case,a break or breaks occur
and that fragment of chromosome is
inverted and rejoined rather than being
lost,Inversions are thus rearrangements
that do not involve loss of genetic material
and,unless the breakpoints disrupt an
important gene,individuals carrying
inversions have a normal phenotype,
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
(3) Chromosome Duplication is just that,a
duplication of a section of a chromosome,
A duplication is sometimes referred
to as a 'partial trisomy',Trisomy refers to
three,Therefore if a duplication exists,
that individual has three copies of that
area instead of two,This means there are
extra instructions (genes) present that can
cause an increased risk for birth defects or
developmental problems,
Medical Genetics
Medical Genetics
Medical Genetics
(4) A ring chromosome can happen in two
ways,
One is demonstrated in the picture;
the end of the p and q arm breaks off and
then stick to each other,The blue parts of
each are lost thus resulting in loss of
information,Second,the ends of the p
and q arm stick together (fusion),usually
without loss of material,However the ring
can cause problems when the cell divides
and can cause problems for the individual,
Medical Genetics
Medical Genetics
Medical Genetics
(5) Translocations are
chromosomal abnormalities which
occur when chromosomes break and
the fragments rejoin to other
chromosomes,
Medical Genetics
There are many structurally
different types of translocations,As
with inversions,there is no loss of
genetic material,although the
breakpoint can cause disruption of a
critical gene or juxtapose pieces of
two genes to create a fusion gene
that induces cancer,
Medical Genetics
In general however,the problem
with translocations occurs during
meiosis and is manifest as reductions
in fertility,
Medical Genetics
Reciprocal translocations
In a reciprocal translocation,two non-
homologous chromosomes break and
exchange fragments,
Medical Genetics
Medical Genetics
Medical Genetics
Individuals carrying such
abnormalities still have a balanced
complement of chromosomes and
generally have a normal phenotype,
but with varying degrees of
subnormal fertility,
Medical Genetics
Medical Genetics
Translocations are thus
heritable and can be perpetuated in
populations,
Medical Genetics
Centric Fusions
A centric fusion is a translocation in
which the centromeres of two acrocentric
chromosomes fuse to generate one large
metacentric chromosome,They are also
often called Robertsonian
translocations,although that term is
used by purists to designate a very similar
but distinct translocation in which one of
the two centromeres is lost,
Medical Genetics
The karyotype of an individual
carrying a centric fusion has one less
than the normal diploid number of
chromosomes,
Medical Genetics
,
Medical Genetics
Medical Genetics
Meiosis in animals carrying a
centric fusion chromosome involves
formation of trivalents,which is
certainly an abnormal structure,
Medical Genetics
In general,centric fusions appear
to cause a mild reduction in fertility
(5-15%),much less severe than in
the case of reciprocal translocations,
Medical Genetics
(6)isochromosome
Medical Genetics
Medical Genetics
(7) Chromosome breakage and re-
union
Structural aberrations are almost
formed by Chromosome breakage
and re-union,
Medical Genetics
Medical Genetics
Medical Genetics
10 人类染色体畸变
chromosome aberration
Medical Genetics
Any type of change in the
chromosome structure or number
(deficiencies,duplications,
translocations,inversions,etc.),
Medical Genetics
Although it can be a mechanism
for enhancing genetic diversity,such
alterations are usually fatal or ill-
adaptive,especially in animals,
Medical Genetics
1,factors inducing chromosome aberration
A,Ionizing radiation
Ionizing radiation produces
rearrangements of the genome,
Medical Genetics
Medical Genetics
When irradiation occurs during
the G0/G1 phase of the cell cycle,
large-scale rearrangements appear
as exchange-type chromosome
aberrations at the next mitosis,Such
aberrations can alter cellular
phenotypes,and are important in
various areas of biology,
Medical Genetics
Medical and public-health
applications include perinatal
diagnostics characterization of specific
cancer types,carcinogenesis risk
estimation,radiation biodosimetry and
radiotherapeutic treatment planning,
Medical Genetics
Analyzing chromosome aberrations
helps characterize repair/misrepair
pathways involved in the processing of
DNA damage,Ionizing radiation has some
unique features as a probe of such
pathways,Compared to other genotoxic
agents,it produces copious quantities of
DNA double strand breaks (DSBs),and its
timing can be controlled more accurately,
Medical Genetics
Moreover,initial radiation
damage has a discrete,stochastic
character that can be modulated by
using different kinds of radiation (e.g,
a -particles versus x-rays) having
different ionization densities,
Medical Genetics
The spectrum of different
radiation-induced chromosome
aberrations is informative about the
geometry of chromosomes during
interphase,and vice versa,
Medical Genetics
Chromosomal instability,in which
new aberrations (though often not of
the type characteristic of G0/G1
damage) continue to arise many
generations after irradiation,
represents a form of genomic
instability,and genomic instability is
prominent during neoplastic
progression,
Medical Genetics
B,chemical mutagen
A kind of substances,such as
drugs or toxins,that causes
chromosomal aberrations of living
organisms,or increase the rate of
mutation,
Medical Genetics
2,chromosomal aberrations
A,chromosome numerical
aberration
Numerical aberration is a change
in the number of chromosomes from
the normal number characteristic of
the human beings,
Medical Genetics
(1) Euploidy is the condition of
having a normal number of
structurally normal
chromosomes,
Euploid human females have 46
chromosomes (44 autosomes and
two X chromosomes),
Medical Genetics
Polyploidy is a multiple of the
haploid chromosome number (n)
other than the diploid number (i.e.,
3n,4n and so on),
Medical Genetics
(2) Aneuploidy is the condition of
having less than or more than the
normal diploid number of
chromosomes,and is the most
frequently observed type of
cytogenetic abnormality,
In other words,it is any deviation from
euploidy,although many authors restrict
use of this term to conditions in which
only a small number of chromosomes are
missing or added,
Medical Genetics
Generally,aneuploidy is recognized
as a small deviation from euploidy for
the simple reason that major
deviations are rarely compatible with
survival,and such individuals usually
die prenatally,
Medical Genetics
The two most commonly
observed forms of aneuploidy are
monosomy and trisomy,
Medical Genetics
Monosomy is lack of one of a pair
of chromosomes,An individual having
only one chromosome 6 is said to have
monosomy 6,A common monosomy seen
in many species is X chromosome
monosomy,also known as Turner's
syndrome,Monosomy is most commonly
lethal during prenatal development,
Medical Genetics
Trisomy is having three
chromosomes of a particular type,A
common autosomal trisomy in humans in
Down syndrome,or trisomy 21,in which a
person has three instead of the normal
two chromosome 21s,Trisomy is a specific
instance of polysomy,a more general
term that indicates having more than two
of any given chromosome,
Medical Genetics
Another type of aneuploidy is
triploidy,A triploid individual has
three of every chromosome,that is,
three haploid sets of chromosomes,
A triploid human would have 69
chromosomes (3 haploid sets of 23),
Medical Genetics
Production of triploids seems to
be relatively common and can occur
by,for example,fertilization by two
sperm,
Medical Genetics
However,birth of a live triploid is
extraordinarily rare and such
individuals are quite abnormal,The
rare triploid that survives for more
than a few hours after birth is almost
certainly a mosaic,having a large
proportion of diploid cells,
Medical Genetics
(3) Chromosome non-disjunction
The failure of a pair of homologous
chromosomes to separate properly during
meiosis,The failure of homologues (at
meiosis) or sister chromatids (at mitosis)
to separate properly to opposite poles,
that is two chromosomes or chromatids go
to one pole and none to the other,
Medical Genetics
Non-disjunction can occur during
meiosis I or meiosis II,An error in
the proper segregation of the
chromosomes during both meiosis I
and II are pictured below,
Medical Genetics
In meiosis I,the error occurs
when the homologous pairs both
travel into the same daughter
cell,The result is two daughter cells
that have two copies of the
chromosome (called disomic cells)
and two cells that are missing that
chromosome (called nullisomic
cells),
Medical Genetics
Non-disjunction in Meiosis I,
Medical Genetics
In meiosis II,the error occurs
when the sister chromatids will not
separate and thus travel into the
same daughter cell,
Medical Genetics
Non-disjunction in Meiosis II,
Medical Genetics
Fertilization following Meiosis I error,
Medical Genetics
Fertilization following Meiosis II error,
Medical Genetics
Medical Genetics
B,Chromosome Structural
Aberration
Structural aberration is a change
in chromosome structure detectable
by microscopic examination of the
metaphase stage of cell division,
observed as deletions and fragments,
intrachanges or interchanges,
Medical Genetics
(1) A chromosome deletion occurs
when the chromosome breaks
and a piece is lost,This of course
involves loss of genetic information
and results in what could be
considered "partial monosomy" for
that chromosome,
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
(2) A related abnormality is a
chromosome inversion,
In this case,a break or breaks occur
and that fragment of chromosome is
inverted and rejoined rather than being
lost,Inversions are thus rearrangements
that do not involve loss of genetic material
and,unless the breakpoints disrupt an
important gene,individuals carrying
inversions have a normal phenotype,
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
(3) Chromosome Duplication is just that,a
duplication of a section of a chromosome,
A duplication is sometimes referred
to as a 'partial trisomy',Trisomy refers to
three,Therefore if a duplication exists,
that individual has three copies of that
area instead of two,This means there are
extra instructions (genes) present that can
cause an increased risk for birth defects or
developmental problems,
Medical Genetics
Medical Genetics
Medical Genetics
(4) A ring chromosome can happen in two
ways,
One is demonstrated in the picture;
the end of the p and q arm breaks off and
then stick to each other,The blue parts of
each are lost thus resulting in loss of
information,Second,the ends of the p
and q arm stick together (fusion),usually
without loss of material,However the ring
can cause problems when the cell divides
and can cause problems for the individual,
Medical Genetics
Medical Genetics
Medical Genetics
(5) Translocations are
chromosomal abnormalities which
occur when chromosomes break and
the fragments rejoin to other
chromosomes,
Medical Genetics
There are many structurally
different types of translocations,As
with inversions,there is no loss of
genetic material,although the
breakpoint can cause disruption of a
critical gene or juxtapose pieces of
two genes to create a fusion gene
that induces cancer,
Medical Genetics
In general however,the problem
with translocations occurs during
meiosis and is manifest as reductions
in fertility,
Medical Genetics
Reciprocal translocations
In a reciprocal translocation,two non-
homologous chromosomes break and
exchange fragments,
Medical Genetics
Medical Genetics
Medical Genetics
Individuals carrying such
abnormalities still have a balanced
complement of chromosomes and
generally have a normal phenotype,
but with varying degrees of
subnormal fertility,
Medical Genetics
Medical Genetics
Translocations are thus
heritable and can be perpetuated in
populations,
Medical Genetics
Centric Fusions
A centric fusion is a translocation in
which the centromeres of two acrocentric
chromosomes fuse to generate one large
metacentric chromosome,They are also
often called Robertsonian
translocations,although that term is
used by purists to designate a very similar
but distinct translocation in which one of
the two centromeres is lost,
Medical Genetics
The karyotype of an individual
carrying a centric fusion has one less
than the normal diploid number of
chromosomes,
Medical Genetics
,
Medical Genetics
Medical Genetics
Meiosis in animals carrying a
centric fusion chromosome involves
formation of trivalents,which is
certainly an abnormal structure,
Medical Genetics
In general,centric fusions appear
to cause a mild reduction in fertility
(5-15%),much less severe than in
the case of reciprocal translocations,
Medical Genetics
(6)isochromosome
Medical Genetics
Medical Genetics
(7) Chromosome breakage and re-
union
Structural aberrations are almost
formed by Chromosome breakage
and re-union,
Medical Genetics
Medical Genetics
Medical Genetics
