性别决定和伴性遗传(英文版)

1、sex determination female:theca) sertoli cells(male:sertoli;female:follicol) related cells,nine genes to be concerned with sexdifferentiation (molecular level),sex-determining gene of sex chromosome: sex-determining region of y chromosome： sry sex-determining region of x chromosome： dax1 sex-determin

2、ing gene on euchromosome: sox（sox3、sox9） amh(mis) wt1 sf1 dmrt1 wnt4,sry(sex-determining region of y chromosome),1.sry play the on-off action，and the gene of man have the function of transcription。sry can restrain the development ofmullerian duct by dominant the secretion of some thing;it also can p

3、roduce male structures. 2.if female be short of sry,the dss of x chromosome will transcription,so to promote the development of ovary.,dax1 (dosage sensitive sex-reversal-adrenal hypoplasia congenital- critical region of the x chromosome gene 1),dax1stem from two genetic locis of x chromosome which

4、name is dss and ahc; dax1 protein is affected by retinoic acid receptor negative regulator of transcription factors, there is the function of ovary-mediated.,sox (sry-type hmg box ),sox9 (sry-type hmg box 9) sox9 have the rule both on skeletal development and sex determination sox9 initially express

5、ed in both male and female genital ridge,when sry expressed,it will express in the male genital ridge,and then cause podocyte development sox9 have the same function of sry,and if sry gene deletion,sox9 will induce male differentiation to ensure normal development of male sox3 (sry-type hmg box 3) s

6、ox3is the only gene which lie in x chromosome.this gene associated with the sry gene,sox3 and sry genes may be allele.it can encode sry-binding protein in male sex embryos,and play the rule in embryonic central nervous system development and undifferentiated gonad,wt1（wilmstumor suppressor gene 1）,i

7、nhibition of cell division and differentiation,and is concerned with mesenchymal cells form ovarian. it may control sry at the beginning of sexdifferentiation,and activate a series of genes,then result in the formation of testis.,amh（anti-mullerian hormone）,amhis an important factor in male differen

8、tiation,gene expression of amh degrade mullerian duct in male body,then prevent it from developing into the female genital organs.,sf1（steroidogenic factor 1）, regulate the gene expression both in gonad and adrenal gland; participate in transcriptional regulation of many genes of steroid generation,

9、reproduction,and male sexual differentiation.,wnt4(wingless-related mmtv integration site 4), potential ovarian determining gene of euchromosome.at beginning it expressed in renal mesenchymal and undifferentiated gonad. it can inhibite male sexual differentiation and synthetic hormone androgen by fe

10、male gonad.,developmental mechanisms of sexuality,sex-linked inheritance,01,02,03,conception,separation of the disease,case analysis,conception,sexlinked inheritance: a genetic pattern which in the genetic process,some trait of the offsprings are controlled by the gene of sex chromosomes.,the separa

11、tion of disease,xlinked dominant inheritable disease xlinked recessive inheritable disease ylinked inheritable disease,xlinked dominant inheritable disease,characteristic: paroxysm will happen if there have the disease-causing gene,and the paroxysm of women is about twice as much as men. if a man to

12、 be sicked,at least one of his parents also sick(except genic mutation) it can inheritant for successive generations,but the patients daughter who is healthy will not genetic to the next generation man will genetic to his daughter while woman will genetic to both her daughter and son ,and the probab

13、ility is equal,some cases:,alport syndrome（as) vitamind-resi-stantrickets pseudohypertrophic muscular dystrophy,case analysis of xlinked dominant inheritable disease,alport syndrome（as) hereditary nephritis (alport syndrome, as) is a serious genetic disease that can lead to end-stage renal failure，s

14、o far, a number of different regions and ethnic groups have reported to find as.,genetic approach,the genetic approach of as is heterogeneous,and it is reported that the disease-causing gene is col4an, which is the gene of encoding basement membrane collagen type chain , the genetic approach and gen

15、e targeting of alport syndrome see the chart overleaf,pathogenesis,it is not clear of the pathogenesis of hereditary nephritis，and it presumably because of gene mutation,it result in abnormal about chain ,undermine the formation of type collagen molecules,thus changing the structure of basement memb

16、rane,impacting glomerular filtration rate, resulting in decreased kidney function.,xlinked recessive inheritable disease,characteristic: the probability for man to be affected is too much bigger than woman if the woman is healthy,her children will healthy,but if she is sick,her father and her son wi

17、ll also sick,some cases,hemophilia achromatopsia glucose6phosphate dehydrogenase deficienly ectodermal dysplasia i,case analysis of xlinked recessive inheritable disease,hemophilia hemophilia is an x chromosome linked, coagulation factor viii (fviii) or clotting factor meter ix (fix) gene defect cau

18、sed severe coagulation disorders,the separation of hemophilia,1.hemophilia a（antihemophilic globulin,ahg or factor deficiency） 2.hemophilia b（ptc or factor deficiency) 3.hemophilia c（pta）or plasma thromboplastic antecedent deficiency ,factor deficiency) 4.von willebrand disease,therapeutic method,cl

19、otting factor replacement therapy (traditional method) with fresh whole blood, plasma or fresh frozen plasma (ffp) replacement clotting factor,in order to make up for the lack of clotting factor the defect:transfusions of replacement of blood, plasma or fresh frozen plasma are large.it have the risk

20、 to lead to high blood volume and the tendency to increased bleeding genetherapy refers to the exogenous normal gene into the target cells to correct or compensate for genetic defects and abnormalities caused by disease, in order to achieve the treatment objectives,genetherapy,vector system,the choi

21、ce of target cells,the direction of new treatments,immune response,vector system which is needed:,viral vector retrovirus,rv adenovirus,av adeno-associated virus,aav lentivirus,lv non-viral gene transfer,the choice of target cells,liver skeletal muscle cells fibroblasts keratinocyte bone marrow stro

22、mal cells,immune response,in the process of gene therapy can produce alternative for exogenous inhibitory factor antibody，the combination of inhibitory antibodies and clotting factor molecules with a specific region can change its structure, so tmake it inactivation .the production of inhibitory antibodies and the type of mutation is concerned with the type of genic mutation,the direction of new treatments,pre-messenger rna, pre-mrna bl