Medical Genetics
09 人类染色体
human chromosome
Medical Genetics
A chromosome is the visible
state of genetic material during a
phase of the division of the cell
(metaphase),
Medical Genetics
Humans have 23 pairs of
chromosomes,which makes the
diploid number 46,The diploid
number is the number of
chromosomes of a normal cell,
Medical Genetics
The haploid number is the
number of chromosomes in a
gamete,Usually,the diploid
number is twice the haploid
number,
Medical Genetics
The number of chromosomes
varies depending on the species,
Medical Genetics
1,chromatin
Chromatin is that portion of the
cell nucleus which contains all of the
DNA of the nucleus in animal cells,(A
small amount of special DNA is also
found in the mitochondria of the cell
cytoplasm outside of the cell
nucleus.)
Medical Genetics
Medical Genetics
A,heterchromatin and euchromatin
The degree of condensation of the nuclear DNA is
variable,
Strongly condensed DNA is called heterochromatin,
Less condensed one euchromatin,
Heterochromatin is stained more intense than
euchromatin by certain nuclear dyes,
Medical Genetics
Heterochromatin is the condensed
form of chromatin organization,It is
seen as dense patches of chromatin,
Medical Genetics
Abundant heterochromatin is
seen in resting,or reserve cells such
as small lymphocytes (memory cells)
waiting for exposure to a foreign
antigen,Heterochromatin is
considered transcriptionally
inactive,
Medical Genetics
There are two types of
heterochromatin,Facultative
heterochromatin and Constitutive
heterochromatin,
Medical Genetics
Facultative heterochromatin is
condensed chromatin that unfolds
and becomes transcriptionally active
during some portion of the cell cycle
(Barr body),
Medical Genetics
Constitutive heterochromatin
refers to the chromatin that remains
transcriptionally inert during the
entire cell cycle,
Medical Genetics
The bulk of constitutive
heterochromatin is composed of non-
coding DNA sequences that are
repeated hundreds of thousands or
even millions of times,
Medical Genetics
Medical Genetics
Euchromatin is threadlike,
delicate,It is most abundant in
active,transcribing cells,Thus,
the presence of euchromatin is
significant because the regions of
DNA to be transcribed or duplicated
must uncoil before the genetic code
can be read,
Medical Genetics
Condensation and decondensation
of the DNA are at least partially
reversible processes,Each DNA
segment that has to be replicated or
transcribed has to be decondensed
during this time,
Medical Genetics
The highest degree of
condensation can be found in the
chromosomes (mitosis,meiosis)
during cell division,
Medical Genetics
Medical Genetics
Medical Genetics
B,the nucleosome
The fundamental structural unit
of chromatin is an assemblage,
called the nucleosome,composed of
five types of histones (designated H1,
H2A,H2B,H3,and H4) and DNA,
Medical Genetics
A nucleosome consists of
approximately 1.8 turns of DNA
wound around a core particle of
histone proteins,The core particle is
a roughly heart-shaped octamer of 4
types of histones,two each of the
H2A,H2B,H3,and H4 proteins,
Medical Genetics
The DNA between two
nucleosomes is called the linker
segment,This linker segment gives
unfolded chromatin a beads-on-a-
string appearance (the nucleosomes
are the beads),
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
DNA is bound to the histones
through electrostatic forces between
the negatively charged phosphate
groups in the DNA backbone and
positively charged amino acids (e.g.,
lysine and arginine) in the histone
proteins,
Medical Genetics
At times,histone proteins are
modified by the addition of acetyl,
methyl,or phosphate groups,and
this alters the strength of the
bonding between the histones and
DNA,
Medical Genetics
Modifications such as these are
usually associated with the
regulation of biological processes
such as DNA replication,gene
expression,chromatin assembly and
condensation,and cell division,
Medical Genetics
C,Scaffold-radial loop structure
model
Chromatin refers
to proteins that help
organize the long
DNA molecule,The
protein supports and
organizes small loops
of DNA,
Medical Genetics
Medical Genetics
2.Chomosome
At some point during the cell
division process,the chromatin will
be packaged tightly enough that we
are able to visualize distinct
chromosomes under the light
microscope,
Medical Genetics
A,chromosome biology
The chromosomes do not actually
become visible in the eukaryotic cell
until after the DNA is replicated,So,
a newly-visible chromosome is a
duplicated chromosome,and
contains two copies of the DNA
double helix,
Medical Genetics
These chromosomes are
composed of two threads of
chomatin,called chromatids,which
are attached to one another at the
centromere of the chromosome,The
2 chromatids that make up a
duplicated chromosome are the
products of DNA replication,and are
known as sister chromatids,
Medical Genetics
Organisms that reproduce through
sexual reproduction have two copies of
each type of chromosome in their somatic
(body) cells,one inherited from each of
their parents,Such organisms are said to
be diploid,whereas cells with only one
copy of each type of chromosome (such as
germ cells or gametes) are said to be
haploid,
Medical Genetics
Cytogenetic
analyses are
almost always
based on
examination of
chromosomes
fixed during
mitotic
metaphase,
Medical Genetics
Metaphase chromosomes differ
from one another in size and shape,
and the absolute length of any one
chromosome varies depending on
the stage of mitosis in which it was
fixed,
Medical Genetics
A model of a chromosome during metaphase
Medical Genetics
However,the relative position of the
centromere is constant,which means
that that the ratio of the lengths of the
two arms is constant for each
chromosome,This ratio is an important
parameter for chromosome identification,
and also,the ratio of lengths of the two
arms allows classification of chromosomes
into several basic morphologic types,
Medical Genetics
Medical Genetics
Similar chromosomes inherited
from different parents are known as
homologous chromosomes,with
corresponding homologous
chromatids,These chromosomes are
similar in that they have the same
genes at the same locations on the
chromosome,but may have different
forms (or alleles) of those genes,
Medical Genetics
Medical Genetics
B,chromosome staining
Medical Genetics
Medical Genetics
人类染色体非显带核型图
Medical Genetics
Chromosome banding
? Q banding
? G banding
? R banding
? T banding
? C banding
? N banding
? High resolution banding
Medical Genetics
Medical Genetics
G banding (model)
Medical Genetics
Model banding
Medical Genetics
Model banding
Medical Genetics
Chromosome 1
Medical Genetics
? X chromosome
? Contains over
1400 genes
? Contains over
150 million
base pairs,of
which
approximately
95% have
been
determined
Medical Genetics
C显带核型图
Medical Genetics
3,Sex chromosome and sex-determination
Humans usually have 46
chromosomes per diploid cell
consisting of 22 sets of autosomes
and a set of sex chromosomes -
either XX or XY,In the usual course
of events,individuals with the
karyotype 46,XX are female and
individuals with 46,XY,are male,
Medical Genetics
The question arises as to how the
sex of an individual is determined,Is
sex determined by the number of X
chromosomes - with one X you are
male or with 2 X's you are female?
Medical Genetics
Or is sex determined by the
presence or absence of the Y
chromosome - the presence of a Y
makes for a male or the absence of a
Y produces a female?
Medical Genetics
The answer was provided by
individuals resulting from non-
disjunction of the sex chromosomes,
Medical Genetics
Some individuals have 45
chromosomes and have only one X
chromosome; other individuals have
47 chromosomes and have two X
chromosomes and a Y,
Medical Genetics
Chromosome
Constitution
Name of
Syndrome
Sex of
Individual
Frequency in
Population
46,XX Normal Female 0.511*
46,XY Normal Male 0.489*
45,XO Turner's Syndrome Female 1/5,000
47,XXY Klinefelter's Syndrome Male 1/700
Female (46,XX) and Male (46,XY) frequencies taken from the US Census projection
Medical Genetics
Usually,a woman has two X
chromosomes (XX) and a man one X
and one Y (XY),
Medical Genetics
However,both male and female
characteristics can sometimes be
found in one individual,and it is
possible to have XY women and XX
men,
Medical Genetics
Analysis of such individuals has
revealed some of the molecules
involved in sex determination,
including one called SRY,which is
important for testis formation,
Medical Genetics
SRY (which stands for sex-
determining region Y gene) is found
on the Y chromosome,In the cell,it
binds to other DNA and in doing so
distorts it dramatically out of shape,
Medical Genetics
This alters the properties of the
DNA and likely alters the expression
of a number of genes,leading to
testis formation,
Medical Genetics
Most XX men who lack a Y
chromosome do still have a copy of
the SRY region on one of their X
chromosomes,This copy accounts for
their maleness,However,because
the remainder of the Y chromosome
is missing they frequently do not
develop secondary sexual
characteristics in the usual way,
Medical Genetics
? Contains over 200 genes
? Contains over 50 million base pairs,
of which approximately 50% have
been determined
Medical Genetics
Medical Genetics
4,chromosomal polymorphism
Polymorphism is a general concept in
biology,referring to a more than one
version of a trait being actively present in a
population,
Medical Genetics
Chomosomal polymorphism refers to
the condition where one species contains
members with varying chromosome
counts or shapes,In most cases,the
difference in chromosome counts is the
result of a single gene undergoing fission,
where it splits into two smaller
chromosomes,or two undergoing fusion,
where two chromosomes join to form one,
Medical Genetics
5,An International System for Human
Cytogenetic Nomenclature
Symbols and abbreviated terms used
in the description of chromosomes and
chromosomal abnormalities are listed
below,For a detailed discussion of these
terms,consult ISCN (1995),An
International System for Human
Cytogenetic Nomenclature,Mitelman,F
(ed); S,Karger,Basel,1995,
Medical Genetics
? add additional material of unknown origin
? arrow (->) from - to,in detailed system
? brackets,square ([]) surround the number of
cells
? cen centromere
? colon,single (:)break,in detailed system
? colon,double (::)break and reunion,in detailed
system
? comma (,)separates chromosome numbers,sex
chromosomes,and chromosome
abnormalities
? decimal point (.) denotes sub-bands
Medical Genetics
? del deletion
? de novo designates a chromosome
abnormality which has not
been inherited
? der derivative chromosome
? dic dicentric
? dup duplication
? fra fragile site
? h heterochromatin,constitutive
? hsr homogeneously staining region
? i isochromosome
Medical Genetics
? ins insertion
? inv inversion
? mar marker chromosome
? mat maternal origin
? minus sign (-)loss
? p short arm of chromosome
? Parenthese ssurround structurally altered
chromosome and breakpoints
? pat paternal origin
Medical Genetics
? plus sign (+) gain
? q long arm of chromosome
? question mark (?) questionable
identification of a chromosome or
chromosome structure
? r ring chromosome
? rec recombinant chromosome
? s satellite
? sce sister chromatid exchange
Medical Genetics
? semicolon (;) separates altered
chromosomes and breakpoints in
structural rearrangements involving
more than one chromosome
? slant line (/) separates clones
? t translocation
? ter terminal (end of chromsome)
? upd uniparental disomy
Medical Genetics
In Situ Hybridization,Symbols and Abbreviations
? minus sign (-) absent from a specific chromosome
? plus sign (+) present on a specific chromosome
? multiplication sign (x) precedes the number of
signals seen
? period (.) separates cytogenetic observations from
results of in situ hybridization
? semicolon (;) separates probes on different
derivative chromosomes
? fish fluorescence in situ hybridization
? ish in situ hybridization; when used without a prefix
applies to chromsomes (usually metaphase or
prometaphase) of dividing cells
? wcpwhole chromosome paint
09 人类染色体
human chromosome
Medical Genetics
A chromosome is the visible
state of genetic material during a
phase of the division of the cell
(metaphase),
Medical Genetics
Humans have 23 pairs of
chromosomes,which makes the
diploid number 46,The diploid
number is the number of
chromosomes of a normal cell,
Medical Genetics
The haploid number is the
number of chromosomes in a
gamete,Usually,the diploid
number is twice the haploid
number,
Medical Genetics
The number of chromosomes
varies depending on the species,
Medical Genetics
1,chromatin
Chromatin is that portion of the
cell nucleus which contains all of the
DNA of the nucleus in animal cells,(A
small amount of special DNA is also
found in the mitochondria of the cell
cytoplasm outside of the cell
nucleus.)
Medical Genetics
Medical Genetics
A,heterchromatin and euchromatin
The degree of condensation of the nuclear DNA is
variable,
Strongly condensed DNA is called heterochromatin,
Less condensed one euchromatin,
Heterochromatin is stained more intense than
euchromatin by certain nuclear dyes,
Medical Genetics
Heterochromatin is the condensed
form of chromatin organization,It is
seen as dense patches of chromatin,
Medical Genetics
Abundant heterochromatin is
seen in resting,or reserve cells such
as small lymphocytes (memory cells)
waiting for exposure to a foreign
antigen,Heterochromatin is
considered transcriptionally
inactive,
Medical Genetics
There are two types of
heterochromatin,Facultative
heterochromatin and Constitutive
heterochromatin,
Medical Genetics
Facultative heterochromatin is
condensed chromatin that unfolds
and becomes transcriptionally active
during some portion of the cell cycle
(Barr body),
Medical Genetics
Constitutive heterochromatin
refers to the chromatin that remains
transcriptionally inert during the
entire cell cycle,
Medical Genetics
The bulk of constitutive
heterochromatin is composed of non-
coding DNA sequences that are
repeated hundreds of thousands or
even millions of times,
Medical Genetics
Medical Genetics
Euchromatin is threadlike,
delicate,It is most abundant in
active,transcribing cells,Thus,
the presence of euchromatin is
significant because the regions of
DNA to be transcribed or duplicated
must uncoil before the genetic code
can be read,
Medical Genetics
Condensation and decondensation
of the DNA are at least partially
reversible processes,Each DNA
segment that has to be replicated or
transcribed has to be decondensed
during this time,
Medical Genetics
The highest degree of
condensation can be found in the
chromosomes (mitosis,meiosis)
during cell division,
Medical Genetics
Medical Genetics
Medical Genetics
B,the nucleosome
The fundamental structural unit
of chromatin is an assemblage,
called the nucleosome,composed of
five types of histones (designated H1,
H2A,H2B,H3,and H4) and DNA,
Medical Genetics
A nucleosome consists of
approximately 1.8 turns of DNA
wound around a core particle of
histone proteins,The core particle is
a roughly heart-shaped octamer of 4
types of histones,two each of the
H2A,H2B,H3,and H4 proteins,
Medical Genetics
The DNA between two
nucleosomes is called the linker
segment,This linker segment gives
unfolded chromatin a beads-on-a-
string appearance (the nucleosomes
are the beads),
Medical Genetics
Medical Genetics
Medical Genetics
Medical Genetics
DNA is bound to the histones
through electrostatic forces between
the negatively charged phosphate
groups in the DNA backbone and
positively charged amino acids (e.g.,
lysine and arginine) in the histone
proteins,
Medical Genetics
At times,histone proteins are
modified by the addition of acetyl,
methyl,or phosphate groups,and
this alters the strength of the
bonding between the histones and
DNA,
Medical Genetics
Modifications such as these are
usually associated with the
regulation of biological processes
such as DNA replication,gene
expression,chromatin assembly and
condensation,and cell division,
Medical Genetics
C,Scaffold-radial loop structure
model
Chromatin refers
to proteins that help
organize the long
DNA molecule,The
protein supports and
organizes small loops
of DNA,
Medical Genetics
Medical Genetics
2.Chomosome
At some point during the cell
division process,the chromatin will
be packaged tightly enough that we
are able to visualize distinct
chromosomes under the light
microscope,
Medical Genetics
A,chromosome biology
The chromosomes do not actually
become visible in the eukaryotic cell
until after the DNA is replicated,So,
a newly-visible chromosome is a
duplicated chromosome,and
contains two copies of the DNA
double helix,
Medical Genetics
These chromosomes are
composed of two threads of
chomatin,called chromatids,which
are attached to one another at the
centromere of the chromosome,The
2 chromatids that make up a
duplicated chromosome are the
products of DNA replication,and are
known as sister chromatids,
Medical Genetics
Organisms that reproduce through
sexual reproduction have two copies of
each type of chromosome in their somatic
(body) cells,one inherited from each of
their parents,Such organisms are said to
be diploid,whereas cells with only one
copy of each type of chromosome (such as
germ cells or gametes) are said to be
haploid,
Medical Genetics
Cytogenetic
analyses are
almost always
based on
examination of
chromosomes
fixed during
mitotic
metaphase,
Medical Genetics
Metaphase chromosomes differ
from one another in size and shape,
and the absolute length of any one
chromosome varies depending on
the stage of mitosis in which it was
fixed,
Medical Genetics
A model of a chromosome during metaphase
Medical Genetics
However,the relative position of the
centromere is constant,which means
that that the ratio of the lengths of the
two arms is constant for each
chromosome,This ratio is an important
parameter for chromosome identification,
and also,the ratio of lengths of the two
arms allows classification of chromosomes
into several basic morphologic types,
Medical Genetics
Medical Genetics
Similar chromosomes inherited
from different parents are known as
homologous chromosomes,with
corresponding homologous
chromatids,These chromosomes are
similar in that they have the same
genes at the same locations on the
chromosome,but may have different
forms (or alleles) of those genes,
Medical Genetics
Medical Genetics
B,chromosome staining
Medical Genetics
Medical Genetics
人类染色体非显带核型图
Medical Genetics
Chromosome banding
? Q banding
? G banding
? R banding
? T banding
? C banding
? N banding
? High resolution banding
Medical Genetics
Medical Genetics
G banding (model)
Medical Genetics
Model banding
Medical Genetics
Model banding
Medical Genetics
Chromosome 1
Medical Genetics
? X chromosome
? Contains over
1400 genes
? Contains over
150 million
base pairs,of
which
approximately
95% have
been
determined
Medical Genetics
C显带核型图
Medical Genetics
3,Sex chromosome and sex-determination
Humans usually have 46
chromosomes per diploid cell
consisting of 22 sets of autosomes
and a set of sex chromosomes -
either XX or XY,In the usual course
of events,individuals with the
karyotype 46,XX are female and
individuals with 46,XY,are male,
Medical Genetics
The question arises as to how the
sex of an individual is determined,Is
sex determined by the number of X
chromosomes - with one X you are
male or with 2 X's you are female?
Medical Genetics
Or is sex determined by the
presence or absence of the Y
chromosome - the presence of a Y
makes for a male or the absence of a
Y produces a female?
Medical Genetics
The answer was provided by
individuals resulting from non-
disjunction of the sex chromosomes,
Medical Genetics
Some individuals have 45
chromosomes and have only one X
chromosome; other individuals have
47 chromosomes and have two X
chromosomes and a Y,
Medical Genetics
Chromosome
Constitution
Name of
Syndrome
Sex of
Individual
Frequency in
Population
46,XX Normal Female 0.511*
46,XY Normal Male 0.489*
45,XO Turner's Syndrome Female 1/5,000
47,XXY Klinefelter's Syndrome Male 1/700
Female (46,XX) and Male (46,XY) frequencies taken from the US Census projection
Medical Genetics
Usually,a woman has two X
chromosomes (XX) and a man one X
and one Y (XY),
Medical Genetics
However,both male and female
characteristics can sometimes be
found in one individual,and it is
possible to have XY women and XX
men,
Medical Genetics
Analysis of such individuals has
revealed some of the molecules
involved in sex determination,
including one called SRY,which is
important for testis formation,
Medical Genetics
SRY (which stands for sex-
determining region Y gene) is found
on the Y chromosome,In the cell,it
binds to other DNA and in doing so
distorts it dramatically out of shape,
Medical Genetics
This alters the properties of the
DNA and likely alters the expression
of a number of genes,leading to
testis formation,
Medical Genetics
Most XX men who lack a Y
chromosome do still have a copy of
the SRY region on one of their X
chromosomes,This copy accounts for
their maleness,However,because
the remainder of the Y chromosome
is missing they frequently do not
develop secondary sexual
characteristics in the usual way,
Medical Genetics
? Contains over 200 genes
? Contains over 50 million base pairs,
of which approximately 50% have
been determined
Medical Genetics
Medical Genetics
4,chromosomal polymorphism
Polymorphism is a general concept in
biology,referring to a more than one
version of a trait being actively present in a
population,
Medical Genetics
Chomosomal polymorphism refers to
the condition where one species contains
members with varying chromosome
counts or shapes,In most cases,the
difference in chromosome counts is the
result of a single gene undergoing fission,
where it splits into two smaller
chromosomes,or two undergoing fusion,
where two chromosomes join to form one,
Medical Genetics
5,An International System for Human
Cytogenetic Nomenclature
Symbols and abbreviated terms used
in the description of chromosomes and
chromosomal abnormalities are listed
below,For a detailed discussion of these
terms,consult ISCN (1995),An
International System for Human
Cytogenetic Nomenclature,Mitelman,F
(ed); S,Karger,Basel,1995,
Medical Genetics
? add additional material of unknown origin
? arrow (->) from - to,in detailed system
? brackets,square ([]) surround the number of
cells
? cen centromere
? colon,single (:)break,in detailed system
? colon,double (::)break and reunion,in detailed
system
? comma (,)separates chromosome numbers,sex
chromosomes,and chromosome
abnormalities
? decimal point (.) denotes sub-bands
Medical Genetics
? del deletion
? de novo designates a chromosome
abnormality which has not
been inherited
? der derivative chromosome
? dic dicentric
? dup duplication
? fra fragile site
? h heterochromatin,constitutive
? hsr homogeneously staining region
? i isochromosome
Medical Genetics
? ins insertion
? inv inversion
? mar marker chromosome
? mat maternal origin
? minus sign (-)loss
? p short arm of chromosome
? Parenthese ssurround structurally altered
chromosome and breakpoints
? pat paternal origin
Medical Genetics
? plus sign (+) gain
? q long arm of chromosome
? question mark (?) questionable
identification of a chromosome or
chromosome structure
? r ring chromosome
? rec recombinant chromosome
? s satellite
? sce sister chromatid exchange
Medical Genetics
? semicolon (;) separates altered
chromosomes and breakpoints in
structural rearrangements involving
more than one chromosome
? slant line (/) separates clones
? t translocation
? ter terminal (end of chromsome)
? upd uniparental disomy
Medical Genetics
In Situ Hybridization,Symbols and Abbreviations
? minus sign (-) absent from a specific chromosome
? plus sign (+) present on a specific chromosome
? multiplication sign (x) precedes the number of
signals seen
? period (.) separates cytogenetic observations from
results of in situ hybridization
? semicolon (;) separates probes on different
derivative chromosomes
? fish fluorescence in situ hybridization
? ish in situ hybridization; when used without a prefix
applies to chromsomes (usually metaphase or
prometaphase) of dividing cells
? wcpwhole chromosome paint
