性别决定和伴性遗传(英文版).ppt

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1、sex determination&sexlinked inheritanceJi Qiuyan&Wang Dongzhou Dec.1st 2010sex determination&sexlinked inheritancesex determinationconceptionmechanismconceptionsex determination:During embryonic development,a embryonic gonad which still no differentiation,to determine to develop into testes or ovari

2、es in the process.It is to say dioecious biological sex determinism,and it is result from the interaction of genetic,environmental and physiological factors.Main sex chromosomesXYZWXOmechanismFour cell lines in Gonad:germ cellsteroid-producing cells(male:leydig;female:theca)sertoli cells(male:sertol

3、i;female:follicol)related cellsnine 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：DAX1Sex-determining gene on euchromosome:SOX（SOX3、SOX9）AMH(MIS)WT1 SF1 Dmrt1 Wnt

4、4SRY(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 produce male structures.2.If female be short of SRY,the DSS of X chrom

5、osome 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 name is DSS and AHC;DAX1 protein is affected by retinoic acid receptor neg

6、ative 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 expressed in both male and female genital ridge,when sry expressed,it will express in t

7、he 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 maleSOX3 (Sry-type HMG box 3)SOX3is the only gene which lie in X chromosome.This gene associated with the Sry ge

8、ne,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 gonadWt1（Wilmstumor suppressor gene 1）Inhibition of cell division and differentiation,and is concerned with mesenchymal cel

9、ls 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 differentiation,gene expression of AMH degrade Mullerian duct in male body,then prevent it from

10、 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,reproduction,and male sexual differentiation.Wnt4(Wingless-related MMTV integration site 4)

11、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 female gonad.Developmental mechanisms of sexuality sex-linked inheritancesex-linked inheritance01

12、0102020303conceptionconceptionSeparation of the diseaseCase analysisconceptionsexlinked inheritance:A genetic pattern which in the genetic process,some trait of the offsprings are controlled by the gene of sex chromosomes.The separation of diseaseXlinked dominant inheritable diseaseXlinked recessive

13、 inheritable diseaseYlinked inheritable diseaseXlinked dominant inheritable diseasecharacteristic: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 be sicked,at least one of his parents also sick(except genic mutation)it c

14、an 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 probability is equalsome cases:alport syndrome（AS)vitaminD-resi-stantRicketspseudoh

15、ypertrophic muscular dystrophyCase analysis of Xlinked dominant inheritable diseasealport syndrome（AS)Hereditary nephritis(alport syndrome,AS)is a serious genetic disease that can lead to end-stage renal failure，So far,a number of different regions and ethnic groups have reported to find AS.Genetic

16、approachThe 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 Gene targeting of Alport syndrome see the chart overleafpathogenesisIt is not clear of the patho

17、genesis 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 membrane,impacting glomerular filtration rate,resulting in decreased kidney function.Xlinked recessi

18、ve inheritable diseasecharacteristic: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 will also sicksome caseshemophiliaachromatopsiaglucose6phosphate dehydrogenase deficienlyectodermal dy

19、splasia ICase analysis of Xlinked recessive inheritable diseaseHemophilia Hemophilia is an X chromosome linked,coagulation factor VIII(FVIII)or clotting factor meter IX(FIX)gene defect caused severe coagulation disordersThe separation of hemophilia1.hemophilia A（antihemophilic globulin,AHG or factor

20、 deficiency）2.hemophilia B（PTC or factor deficiency)3.hemophilia C（PTA）or plasma thromboplastic antecedent deficiency,factor deficiency)4.von Willebrand disease Therapeutic Methodclotting factor replacement therapy(traditional method)With fresh whole blood,plasma or fresh frozen plasma(FFP)replaceme

21、nt 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 to lead to high blood volume and the tendency to increased bleeding genetherapy refers to the exogenous normal gene into the

22、 target cells to correct or compensate for genetic defects and abnormalities caused by disease,in order to achieve the treatment objectives genetherapy Vector systemThe choice of target cellsThe direction of new treatmentsImmune responseVector system which is needed:Viral vector retrovirus,RV adenov

23、irus,AV adeno-associated virus,AAV lentivirus,LV Non-viral gene transfer The choice of target cellsliver Skeletal muscle cellsFibroblastsKeratinocyteBone marrow stromal cellsImmune responseIn the process of gene therapy can produce alternative for exogenous inhibitory factor antibody，the combination

24、 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 mutationThe direction of new treatmentspre-messenger RNA,pre-mRNAblood

25、 outgrowth endothelial cells,BOECTreatment of genetically modified stem cellsYlinked inheritable diseasecharacteristic:the disease-causing gene is located on Y-chromosome,so these gene can only be transfered along with Y-chromosome,and it also be called holandric inheritancesome cases:webbed toesHai

26、ry earssome preventive measures of genetic diseaseto develop some consultations about hereditycheck out who is the carrier of Disease-causing gene,and prohibit marriages between blood relativespromoting family planningdo prenatal examination and terminate pregnancy of sick fetusto reduce the contaction of mutagens as much as possible.(some examples of mutagens:Nitrites,Herbicides,Caffeine,Antibiotics,etc.)