Interphase chromosome unfold and unwind to become chromatin.

Chromatin and chromosome are the same substance, but they exist in different forms at different cell cycle phases. Chromatin is a combination of unfolded DNA and protein fibers in the nucleus during cell cycle interphase.

Question: How to understand that euchromatin has transcriptional activity while heterochromatin does not have?

Question: How to explain that facultative heterochromatin has no transcriptional activity when in the condensed state, but recovers when in the loose state?

Question: Why is there difference in X chromatin between males and females ? ① X chromatin: in the interphase nucleus, one of the X chromosome of female forms block structure because of inactivation, with diameter of about 1μm, which is named X chromatin.

It was discovered by Barr in 1949 and is also named Barr nucleosome.

② Y chromatin: in the interphase nucleus, 2/3 distal end in long arm of Y chromosome is constitutive heterochromatin, which will emit fluorescence after being dyed with fluorescence dye. Its diameter is about 0.3μm, which is named Y chromatin.

Mary Lyon put forward the hypothesis about X chromosome inactivation in 1961:

A normal female has two X chromosomes, but only one X chromosome has transcriptional activity while the other turns into X chromatin by inactivation in interphase nuclear. In contrast, X chromosome of a normal male does not have heteropycnosis and the male do not have X chromatin. In that way, male and female have similar dose of gene expression product of X chromosomes.

Key points of Lyon hypothesis:

① X chromosome inactivation occurs around the 16th day during the early period of fetal development.

② X chromosome randomly inactivates. The X chromosome that undergoing heteropycnosis can come from mother or father.

③ X chromosome inactivation is fixed. Once a certain X chromosome is determined to be inactive, the X chromosome in all of the daughter cells is always inactive.

④ The number of X chromatin in a cell is equal to the number of X chromosome minus one, and the number of Y chromatin is equal to the number of Y chromosome. It assures that only one X chromosome has transcriptional activity in both female and male, so that the genes in X linkage group has similar dose of gene expression product in both sexes —it is called dosage compensation, which can be used for prediction of fetus sex and identification of numerical abnormality of sex chromosome.

⑤ Although inactivation of X chromosome is random, the one with structural aberrations have a priority to inactivate. However, the normal X chromosome in balanced translocation carrier has a priority to inactivate.

⑥ Not all genes on the inactivated X chromosome can lose activity. One third of human's genes can avoid total deactivation.

Therefore, the more of X chromosomes, the more serious the clinical symptoms is.

Chromatin turns into chromosome through helical condensation during mitotic phase.

Chromosomes are the supercoiled DNA and protein fiber in the mitotic cells, resulting from tightly coiled and folded chromatin.

The number of chromosomes from the same species is relatively constant.

A set of chromosomes in a normal germ cell (sperm or ovum) are called chromosome set.

All of the genes in a chromosome set are called a genome.

A cell that includes only one chromosome set is called haploid.

A cell that includes two chromosome sets is called diploid.

The number of chromosomes in a somatocyte of a normal human is 23 pairs (2n=46 bars), while the number of chromosomes in a sexual cell of a normal human is 23 bars (n=23 bars).

Human chromosomes can be divided into 7 groups. The biggest group is group A and the smallest group is group G. Group A (chromosome number 1~3), group B (chromosome number 4~5), group C (chromosome number 6~12 and X chromosome), group D (chromosome number 13~15), group E (chromosome number 16~18), group F (chromosome number 19~20), group G (chromosome number 21~22 and Y chromosome).

Y chromosome has Quasi Autosomal Region and Y Specific Region.

Quasi Autosomal Region is the homologous region between X chromosome and Y chromosome, located in the short arm ends of both X chromosome and Y chromosome, where X chromosome and Y chromosome can be recombined.

Y Special Region edcodes several genes, which are necessary for gonadal differentiation and male fertility. Of them, one is testis-determining factor (TDF), which plays an important role in switching action.

Sex-determining region Y (SRY) located on the short arm of Y chromosome (Yp11.3), which is the best candidate gene of TDF. The expression product of SRY gene can promote the expression activity of some enzymes and promote to generate androgen which promote testis develop

Some expression products of SRY gene can promote the production of some statin, which could cause the degeneration of ovary and uterus.

According to the size and morphological characteristics, all of the chromosomes in a somatic cell can be arranged to an image, which is called karyotype. Karyotype in a normal female is 46, XX, and in a normal male is 46, XY. 46 chromosomes in human’s somatic cell can be matched into 23 pairs. The two chromosomes in each pair are the same in size and morphology, which are called homologous chromosome, and one is from father while the other from mother. Of 23 pairs of chromosomes, 22 pairs are autosome, which are numbered from 1 to 22; and one pair are sex chromosome, which are XX in females and XY in males.

It is impossible to identify X chromosome and Y chromosome in non-banding karyotype, but it is imaginable to identify gender through the number of chromosomes from group G.

Group G chromosomes belong to the smallest acrocentric chromosomes, including chromosome 21, 22 and chromosome Y. There are five smallest acrocentric chromosomes in male while four in female.

Chromosome specimens are treated with a series of special processes, and are stained with specific dyes, making chromosomes show alternately bright and dark band or deep and light band along the long axis, which are called chromosomal band. After being stained, chromosomes show specific bands respectively, forming banding pattern. Banding patterns of homologous chromosomes are roughly the same.

Q banding: Specimens of chromosome are treated with QM (fluorescent dye quinacrine mustard), then bands with different width and brightness will be observed under fluorescence microscope.

G banding: Specimens of chromosome are treated with alkali or trypsin and then with Giemsa stain, then bands, similar to Q banding, with alternative dark and light stain will be observed under light microscope.

R banding: Specimens of chromosome are treated with phosphate solution and then with Giemsa stain, then it shows the reverse band opposite to G banding.

T banding: Specimens of chromosome are stained with Giemsa after being heated, making chromosome end show specific trachychromatic telomere banding.

C banding: Specimens of chromosome are treated with NaOH or Ba(OH)2 , and then with Giemsa stain, making the constitutive heterochromatin of both centromere and secondary constriction engrain. For example, secondary constriction of chromosome 1, 9, 16 and 2/3 region of distal end in Y chromosome long arm show C band.

N banding: Staining with silver nitrate make satellite of chromosome and nucleolus organizing region (NOR) show black (Ag-NOR). Only the NOR with transcriptional activity can be stained black, what is stained is a kind of acidic protein related to rDNA transcription.

G banding technique is one of the wildly used banding technique. The characteristics of banded chromosomes with alternately bright and dark band or deep and light band is obvious and stable, which can be used to identify every chromosome with reasonable accuracy

The end of short arm of chromosome 1 is lightly stained, which looks like calvities.

The centromere of chromosome 2 is very thin and lightly stained, which looks like snaky waist.

There are symmetrical light bands on both sides of centromere of chromosome 3, which looks like a bow.

There are four dark bands on the long arm of chromosome 4, which looks like bamboo joint.

There is a wide and dark band on the long arm of chromosome 5, which looks like black belt.

There is a wide and light band on the short arm of chromosome 6, which looks like a small white face.

There is a dark band at the end of the short arm of chromosome 7, which looks like a bottle cap.

The two dark bands of the short arm of chromosome 8 are separated by a light band. The last dark band on the long arm is wide, thick and strong.

The lower-part of centromere on chromosome 9 is light-stained, and there are two dark-stained bands on both short arm and long arm, respectively.

There are three dark-stained bands on the long arm of chromosome 10.

The light-stained band near the centromere on the long arm of chromosome 11 is wide.

The light-stained band near the centromere on the long arm of chromosome 12 is narrow.

The lower-part of the long arm of chromosome 13 is dark-stained.

The middle part of the long arm of chromosome 14 is dark-stained, and the distal part has an obvious dark-stained band.

The upper part of the long arm of chromosome 15 is dark-stained.

The centromere of chromosome 16 is dark-stained. There is a light dark-stained band in the short arm, and a rather dark dark-stained band in the long arm.

There is a joint-like dark-stained band on the distal part of the long arm of chromosome 17, which looks like a shackle.

There is a dark-stained band on the proximal end and distal end of chromosome 18, respectively, which is called “white skin with black belly”.

On the two sides of the centromere of chromosome 19 are dark-stained bands, and the rest are light-stained band, which is called black dot in the middle.

There is obvious dark-stained band on the short arm of chromosome 20, and light-stained band on the long arm, which is called top-heavy.

There is a wide and dark-stained band on the long arm of chromosome 21, which looks like a triangle.

There are dark-stained bands on both sides of centromere on chromosome 22, and another narrow dark-stained band in the middle of the long arm, which looks like a badminton.

There are symmetrical dark-stained bands on both sides of X chromosome, like shouldering a pole, which is called shouldering on dark bands).

There are two dark-stained bands on the long arm of Y chromosome, like a gourd.

An International System for Human Cytogenetics Nomenclature (ISCN) prescribes a standard system for distinguishing the region and band of every chromosome.

Landmark: the remarkable characteristics on chromosomes, including the ends of chromosome arms, centromere and some stable bands.

Question: how to understand that the band on Landmark is the first band of the next Region?

Region: the region between two adjacent landmarks. Numbering region starts from centromere.

Region 1 is the two regions near centromere, and is followed by Region 2, Region 3 and Region 4…

Band: Band of chromosome is continuous, so there is no non-band area.

Numbering band starts from centromere, in turn is Band 1, Band 2, Band 3, Band 4, Band 5, Band 6…

When marking a band, what needed to mark in sequence is: chromosome number, arm symbol, region number and band number, without adding space or punctuation within each other.

For example: 1p35 means Band 5, Region 3 on short arm of chromosome l; 14q32 means Band 2, Region 3 on long arm of chromosome 14.

A set of human haploid includes 320 bands.

High Resolution Banding Technique could make a set of chromosome from human haploid show up to 550 to 850 of bands, even more and thinner sub-bands.

Nomenclature of high resolution band is to add a point after the original band and followed by the number of sub-band.

For example: 1p31.1, 1p31.2, 1p31.3 refers to the first, the second and the third sub-band respectively of region 3 on short arm of chromosome 1.

Chromosome aberration refers to the aberration of the number and structure of chromosomes in somatic or stem cells. The essence of chromosome aberration is the increase or decrease in number or position translocation of gene group on chromosome, which causes the genetic material to change and results in the chromosomal abnormality syndrome or chromosome diseases.

Chromosome aberration can be caused by spontaneous or induced aberration.

Many chemical factors (such as drugs, pesticides, toxins and food additives, etc.), physical factors (such as ionizing radiation, radioactive rays [x, alpha, beta, and gamma], etc.) and biological factors (such as mycotoxins, viruses, etc.) and the age of mother can cause chromosomal aberration.

The older a woman’s childbearing age is (over 35 years old), the longer the germ cells stay in mother’s body. It means the germ cells are more affected by various factors, and the chance of chromosomal abnormalities in the children is greater.

Question: why when the age of a childbearing mother is more than 35 years old, the probability of giving birth to a child with chromosomal abnormalities will go up?

Chromosome number aberration refers to the increase or decrease of the whole chromosome group or the number of chromosome, by the standard of human diploid.

(1) Definition

Normal somatic chromosome is diploid (2 chromosome groups), so 2n = 46. Euploid change refers to the increase or decrease of the whole chromosome group.

(2) Types

① Triploid: somatic cells include 3 chromosome groups (3n = 69), and the chromosome number is 69. Of the spontaneous aborted fetus, it accounts for about 18%.

② Tetraploid: somatic cells include 4 chromosome groups (4n = 92), and the chromosome number is 92; Of the spontaneous aborted fetus, it accounts for about 5%.

③ Haploid: somatic cells include only one chromosome groups, n=23. Plants have two types of reproduction: apomixia and patrogenesis, but haploid is not found in either animal or human beings.

(3) Mechanism of Euploid Change

① Dispermy: 1n♂+1n♂+1n♀=3n. A normal ovum fertilize with two normal sperms to form a triploid. Abortion.

② Digyny: 2n♀+1n♂=3n. An abnormal ovum of diploid fertilize with a normal sperm to form a triploid. Abortion.

③ Endoreduplication: DNA replicates twice, but the cell only splits once, so two daughter cells are tetraploid. This is one of the most common characteristics of chromosome abbreviation of cancer cells.

④ Endomitosis: DNA replicates once, but the cell division could not enter anaphase and telophase, so the cell includes 4 chromosome groups, which forms tetraploid.

Question: What is the pathogenesis of triploid? What is the pathogenesis of tetraploid?

(1) Definition

Normal somatic chromosome is diploid, 2n = 46. Aneuploidy change refers to the increase or decrease in only one or a few number of chromosomes.

(2) Types

① Hypodiploid: Decrease of one or a few chromosomes on the base of 2n.

Monosomy: Decrease of only one chromosome in somatic cell, so the chromosome number is: 2n-1=45.

The most common monosomy karyotypes in clinics are as follows:
45, XX(XY), -21
45, XX(XY, -22
45, X

② Hyperdiploid: Increase of one or a few chromosomes on the basis of 2n.

Trisomy: Increase of only one chromosome in somatic cells, the chromosome number is: 2n+1=47.

Polysomy: aneuploidy change more than trisomy, which is often seen in sex chromosome.

Common karyotypes of trisomy in clinics are as follows:
47, XX(XY), +21
47, XX(XY), +22
47, XXY

Common karyotypes of polysomy in clinics are as follows:
48, XXXX

③ Mosaic: It refers that there are two or more than two karyotypes of cells existing simultaneously in an individual, such as 46, XY/47, XXY and 46, XX/45, X.

④ Pseudodiploid: The chromosome number in cells is normal, but some chromosomes are increased and some are decreased in number, but the sum number is not change. It is still 46.

Chromosome chromosome non-disjunction or chromosome elimination occurred in the process of sexual cells maturation or early cleavage of zygote.

① Chromosome non-disjunction in mitosis of germ cell early cleavage can form the mosaic.

Non-disjunction which occurs at early cleavage of zygote can form mosaic. If non-disjunction occurs at the first cleavage stage, it forms mosaic with two cell lines; If non-disjunction occurs after the second cleavage stage, it forms mosaic with three cell lines. The later non-disjunction occurs, the larger proportion of normal diploid cell line accounts for, and the lighter clinical symptoms will be.

② If non-disjunction occurs at meiosis anaphase I, a daughter cell gets a pair of homologous chromosomes (n+1) while the other can’t get any homologous chromosome (n-1). After normal fertilization with sperm, hyperdiploid or hypodiploid will be formed.

③ If non-disjunction occurs between sister chromatid at meiosis anaphase II, a daughter cell gets two sister chromatids (n+1), while the other can’t get any sister chromatid (n-1); Of all of the gametes, n accounts for 1/2, (n+1) accounts for 1/4 and (n-1) accounts for 1/4.

④ Chromosome elimination, also known as chromosome anaphase lap/delay, refers that if a chromosome moves slowly or can’t connect with the spindle fiber, it will remain on the equator and cannot move toward the poles to participate in the formation of a new daughter cell, resulting in chromosome elimination and the formation of hypodiploidy. Chromosome elimination is also a way to form a mosaic.

Question: What is the cause of aneuploidy? What’s the cause of mosaic formation?

Chromosome structural aberration and its karyotype

Chromosome structural aberration: chromosome breaks firstly, and then the broken fragments rejoin. If the broken fragments rejoin at the original site, it is named reunion. If the broken fragments lose or move and rejoin with other fragments, it is named chromosomal rearrangement.

Description method of chromosome structural aberration:

According to ISCN, there are two methods to describe the karyotypes of chromosome structural aberration:.

Simplified type: The total number of chromosomes; the composition of sexual chromosomes; types, symbols or letters of rearranging chromosomes (chromosome number) (breakpoint of chromosome arm’s number, region number, band number). Detailed type: The total number of chromosomes; the composition of sexual chromosomes; types, symbols or letters of rearranging chromosomes (chromosome number) (composition of rearranging chromosome band).

Types of chromosome structural aberration and its karyotype:

Fragments of chromosome are lost, and accordingly the genes containing this fragment are also lost.

① Terminal deletion: Short arm or long arm breaks once without any reconnection, resulting in the fragments without centromere lose.

Simplified karyotype: 46, XX (XY), del (1)(q21)

Detailed karyotype: 46, XX(XY), del (1)(pter→q21)

Verbal description: The distal segment beyond band 1region 2 in the long arm of chromosome 1loses, which is from the end of the short arm to region 2 band 1 of the long arm.

② Interstitial deletion: The same arm breaks twice, then the non-centromere segments between the two breakpoints lose, and the rest of the two fragments reconnect.

Simplified karyotype:

46, XX(XY), del(3)(q21q31)

Detailed karyotype: 46, XX(XY), del(3)(pter→q21::q31→qter)

Verbal description: Band 1 of region 2 and Band 1 of region 3 in the long arm of chromosome 3 break and reconnect; segments between the two breakpoints are lost.

(2) Duplication, Dup

One fragment of a chromosome is increased by one copy or more than one copy, making the genes in the fragment are increased by one copy or more than one copy.. These are caused by unequal crossover between homologous chromosomes or between chromatids, as well as repetitive insertion of genes of homologous chromosomes

If chromosomes break twice, fragments between two breakpoints rotate 180 degrees and rejoin, leading to rearrangement of the sequence of chromosome genes.

① Paracentric inversion: Breakage occurs within one arm (short arm or long arm).

Simplified karyotype: 46, XX(XY), inv(1)(p22p34)

Detailed karyotype: 46, XX(XY), inv(1)(pter→p34::p22→p34::p22→qter)

Verbal description: p22 and p34 of chromosome 1 fracture, the fragment between these two breakpoints reverse and rejoin, forming paracentric inversion chromosome.

② Pericentric inversion: Breakage occurs between two arms (short arm and long arm).

Simplified karyotype: 46, XX(XY), inv(2)(p15p21)

Detailed karyotype: 46, XX(XY), inv(2)(pter→p15::q21→p15::q21→qter)

Verbal description: p15 and q21 of chromosome 2 fracture, the fragment between these two breakpoints reverse and rejoin, forming a pericentric inversion chromosome.

Fragments reconnection occur between non-homologous chromosomes after chromosome breaks.

① Reciprocal translocation

Two non-homologous chromosomes break at the same time, fragments exchange sites and rejoin with each other, forming two derivation chromosomes. If reciprocal translocation does not cause chromosome fragment increase or decrease, it is called balanced translocation.

Simplified karyotype: 46, XX(XY), t(2; 5)(q21; q31)

Detailed karyotype: 46, XX(XY), t(2; 5) (2pter→2q21::5q31→5qter;5pter→5q31::2q21→2qter)

Verbal description: Both band 1 region 2 on the long arm of chromosome 2 and band 1 region 3 on the long arm of chromosome 5 break at the same time, fragments exchange sites and rejoin with each other,, forming two derivation chromosomes.

Tip-off: The chromosome with a larger number, that is chromosome 2 should be described at first. If reciprocal translocation occurs between a sexual chromosome and an autosome, sexual chromosomes should be described at first.

② Robertsonian translocation

Also known as centric fusion. If two acrocentric chromosomes break at the centromere, two long arms joint to form a new derivative chromosome at the centromere, meanwhile two short arms joint to form a small chromosome, which is lost for lack of centromere.

As the lost small chromosome is almost heterochromatin, and the new chromosome derived from two long arms includes almost all of the genes in two chromosomes, the phenotype of Robertsonian translocation is normal, even though the carrier has only 45 chromosomes.

Simplified karyotype: 45, XX(XY), -14, -21, + rob (14; 21)( q10; q10)

Detailed karyotype: 45, XX(XY), -14, -21, + rob (14; 21)(14qter→14q10::21q10→21qter)

Verbal description: Both band 0 region 1 in the long arm of chromosome 14(14q10) and band 1 region 1 in the long arm of chromosome 21(21q10) break at the same time, and two long arms fuse at the centromere, forming a new derivative chromosome including 21q10→qter segment of chromosome 21 and 14q10→qter segment of chromosome 14, with two short arms lost.

③ Insertional translocation

Two nonhomologous chromosomes break at the same time, but only one fragment from one chromosome insert into the non-terminal site of the other chromosome. It can be either forward insertion or reverted insertion (insertion after rotating 180 degrees ).

(5) Ring chromosome, r The long arm and short arm of one chromosome break at the same time, and the middle segments containing centromere rejoin together.

Simplified karyotype: 46, XX(XY), r(2)(p21q31) Detailed karyotype: 46, XX(XY), r(2) (p21→q31)

Verbal description: when p21 and q31 of chromosome 2 break, the fragments beyond breakpoint lose, while the two ends of the middle segment with centromere of p21 and q31 rejoin and form a ring chromosome.

After two chromosomes break at the same time, the ends of two segments with centromere rejoin, and the fragments without centromere are lost.

Simplified karyotype: 46, XX(XY), dic(5;9)(q31;q21)

Detailed karyotype: 46,XX(XY), dic(5;9) (5pter→5q31::9q21→9pter)

Verbal description: q31 of chromosome 5 and q21 of chromosome 9 break at the same time, the ends of two segments with centromere rejoin, in that way form a derivative chromosome with two centromeres.

As transverse fissure of centromere, the two long arms and two short arms form isochromosome respectively, in that way one with two long arms and one with two short arms. The two arms in one chromosome are the same in both shape and structure.

① Isochromosome with two short arms

Simplified karyotype: 46, X, i(Xp)

Detailed karyotype: 46, X, i(X) (pter→cen→pter)

Verbal description: Isochromosome X with two short arms.

② Isochromosome with two long arms

Simplified karyotype: 46, X, i(Xq)

Detailed karyotype: 46, X, i(X) (qter→cen→qter)

Verbal description: Isochromosome X with two long arms.

Chromosomal Diseases, also called Chromosomal Abnormity Syndrom, resulting from the aberration of chromosome number or structure.

The common clinical characteristics of chromosomal diseases are congenital malformation, growth retardation, mental retardation (MR), unusual facial feature and dermal ridge change.

Patients suffering from sexual chromosomal abnormality have internal and external genital deformity, gonadal dysgenesis, secondary sexual characteristics agenesis and so on.

Chromosomal abnormalities often occur in spontaneously aborted fetus, fetus born by women with advanced maternal age, congenital malformation or dysplasia patients, infertility or habitual abortion couples.

The clinical indications of chromosome karyotypes analysis: patients who have special face, dysplasia or persons that contacted with eratogenic factors.

Autosomal diseases result from numerical or structural aberration of chromosome, which account for two thirds of chromosomal diseases. including trisomicsyndrome, monosomy syndrome, partial trisomic syndrome, partial monosomy syndrome and chimera, etc.

(1) Down Syndrome (DS, OMIM #190685)

DS is also called trisomy 21 syndrome or mongolism.

① Incidence rate: newborns account for 1/1000~2/1000, and the incidence rate rise perpendicularly if pregnant women are over 35 years old,.

② Clinical menifestation: mental retardation, developmental retardation, special face, kalmuch type, male infertility and a few occasionally fertility women.

Severity of chimera depends on the proporation of abnormal clone accounts for.

③ Karyotype: 47, XX(XY), +2 (accounts for 92.5% )

Mosaic type: 47, XX(XY), +21/45, XX(XY), -21/46, XX(XY) ( accounts for 2.5%)

(2) Edward syndrome

① Incidence rate: about 1/3500~1/8000 among newborns.

Male: female =1: 4, which relates to the fact that male embryos are hard to develop to birth.

② Clinical menifestation: multiple malformation, ear deformity, special clenched fist position, rocking chair-like club foot, 95 % fetuses will be aborted. 1/3 newborns will die within a month after birth; 50% newborns will die within 2 months; more than 90% newborns will die within 1 year, and few can live to be childhood.

③ Karyotype: 47, XX(XY), +18

Mosaic type: 47, XX(XY), +18/46, XX (XY) ( accounts for 10%)

① Incidence rate: it accounts for about 1/25000 of newborns. It happens to females more than males and associated with mother’s age, which results from non-disjunction of chromosome 13 from mother during first meiotic division.

② Clinical menifestation: Serious malformation, cheilopalatognathus, microcephalia, cyclopia or anophthalmia. 99% of fetuses will be aborted; 45% of newborns will die within a month and 90% will die within six months. Sign of chimera is not that serious.

③ Karyotype: 47, XX(XY), +13( accounts for 80%)

Mosaic type: 47, XX(XY), +13/46, XX(XY)( accounts for 5%)

① Incidence rate: it accounts for 1/50000 of newborns, 1%~1.5% of mentally retarded children; it happens to female more than male and results from chromosomal structural aberration of parent’s germ cells.

② Clinical menifestation: The cry sound of baby sounds like a mew and it is considered to result from throat malformation, laxation and weakness. It is accompanied with serious mental retardation, microcephaly, moon shaped face, orbital hypertelorism and low ear position.

③ Karyotype: 46, XX(XY), del(5)(p15)

Sex chromosomal diseases result from the numerical or structural aberrations of X or Y Sex chromosomes, which account for about 1/3 of chromosomal diseases.

Sex chromosomal disease is not so serious than autosomal disease on clinical manifestation, because chromosome X loses its activity or chromosome Y has little penetrant gene.

(1) Klinefelter syndrome

Resulting from sex chromosome numerical aberration

① Incidence rate: It accounts for 1/1000~2/1000 in male newborns and 1/260 in men who are higher than 180cm, 1/100 in psychopaths or persons imprisoned in penitentiary and 1/10 in infertile male.

② Clinical menifestation: Testicular dysplasia or infertility, poor secondary sex characteristic, infertility, mild to moderate mental retardation. Chimera has the ability to reproduce as one part of testicle is normal.

③ Karyotype: 47, XXY (accounts for 80% )

Mosaic karyotype: 46, XY/47, XXY (accounts for 15%)

④ Mechanism: X chromosome doesn't depart during the process of oogenesis, leading to one abnormal ovum with one more X chromosome and another one that lack one X chromosome, in that way Klin efelter syndrome formed after fertilization.

⑤ Treatment:

I, Treated with androgen during adolescence to maintain male characterization (patient's plasma testosterone amount is only half of normal people.)

II, Mastectomy can improve the mental state of the patients.

(2) Turner syndrome

Resulting from sex chromosomal numerical abnormality

① Incidence rate: 1/5000 of female newborns. It is hard for fetuses to live in uterus and 99% of them will be aborted.

② Clinical menifestation: short stature (120~140cm), low back hairline, 50% webbed neck, cubitus valgus, infantilism of uterus and genitalia, primary amenorrhea, infertility, mental retardation.

Mosaic is better, and the patients with light symptom may have the ability to reproduce.

③ Karyotype: 45, X

Mosaic Karyotype: 45, X/ 46, XX

④ Mechanism: Because of non-disjunction of X and Y chromosome during spermatogenesis, two kinds of sperms are formed: one is with both X and Y chromosomes, the other is without any, which causes Turner syndrome after fertilization.

⑤ Treatment: It can be treated with estrogen during adolescence to promote secondary sex characteristic growth and reproductive organs development. Although it can improve mental state of the patients, it cannot help grow one's height or tackle fertility problem.

It refers that individual gonad, internal and external genitals and secondary sex characteristics have different degrees of amphoteric character.

During sex differentiation or development, genetic or environmental factors make the secretion and metabolism of sex hormone disordered, which may cause gynandromorphism.

As for gynandromorphism which resulted from genetic mutation, although it has normal chromosome, chromosome examination can determine karyotype, which is helpful for diagnosis.

(1) True hermaphroditism

Clinical manifestation patients have both testicle and ovary.

Their internal and external genitals are intersex, and secondary sex characteristics develop abnormally.

Karyotype: 46, XX (accounts for 57%)

46, XY (accounts for 12%)

46, XX/46, XY (accounts for 5%)

(2) Pseudo hermaphroditism

Clinical menifestation: patients only have one gonad, but both external genitals and secondary sex characteristic are androgynous or the opposite sex.

① Female pseudo hermaphroditism

Clinical menifestation: gonad is ovary; internal and external genitals are intersex; secondary sex characteristics tend to be male.

Karyotype: 46, XX

Common cases are congenital adrenal hyperplasia (CAH), which belongs to AR inheritance.

Its gene is located on 6p21.3, with 21 hydroxylase defect and water and salt metabolic disturbance.

② Male pseudo hermaphroditism

Clinical menifestation: gonad is testicle; internal and external genitals are intersex; secondary sex characteristics are feminine.

Karyotype: 46, XY

Common cases are androgen insensitivity syndrome (AIS), which belongs to XR inheritance.

Androgen receptor gene mutation on X chromosome causes target cell to be insensitivity to androgen. Secondary sex characteristics are female or intersex.

Patient’s karyotype is totally contrary to the phenotype.

① XX male syndrome

2/3 medical cases of XX male syndrome can detect SRY gene mutation. The clinical menifestation is like Klinefelter syndrome.

② XY female syndrome

15% of medical cases of XY female syndrome can detect SRY gene mutation. Gonad looks like streak. External genitals are feminine. Secondary sex characteristic cannot develop. Patients are slim or tall and plump, whose breasts stop growing and have primary amenorrhea.