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1、Medical Genetics Research Building A-7098820-8274 11/ User name and password:geneticsMing Qi 祁鳴, PhD, FACMGHUGO LecturerCAP InspectorZJU Center for Genetic & Genomic MedicineJames Watson Institute of Genomic Sciences& Medical School of Zhejiang UniversityDepartment of Pathology and Lab. Med.Universi

2、ty of Rochester Medical CenterChapter 1 Genetics and Medical ScienceTo medicine, this is the age of human genetics. Achievements in genetics and genomics have changed the infrastructure of medicine.Human and medical genetics are turning into the corner stone of all biomedical sciences in the name of

3、 molecular medicine or genomic medicine.Courtesy from Eric Green, Director, NHGRIDiagnosis & ManagementDisease / PhenotypeGeneChapter 1 Genetics and Medical ScienceLeroy Hood on the FutureMy prediction is that within 10 years, we will have a predictive medicine that will have two separate components

4、. the ability to sequence every humans genome for less than $1,000. predictive health histories for each individual from the varying genes that come from that sequencing have a little hand-held nanotechnology device that will prick your finger and make a thousand measurements and by wireless, send t

5、hat to a server. It will analyze all your past records. Goals of Medical GeneticsAccurate diagnosisPrecise classificationElucidation of basic defectEffective therapy Prevention Goals of Medical GeneticsAccurate diagnosisPrecise classificationElucidation of basic defectPrevention Effective therapyGoa

6、ls of Medical GeneticsAccurate diagnosisPrecise classificationElucidation of basic defectPrevention Effective therapyGoals of Medical GeneticsAccurate diagnosisPrecise classificationElucidation of basic defectEffective therapy Prevention Goals of Medical GeneticsAccurate diagnosisPrecise classificat

7、ionElucidation of basic defect Effective therapyPrevention1.1 The concepts of Genetics in MedicineThe Concept of Gene What is Familial Disease What is Congenital Disease What is Inherited Disease or Genetic Disease The relationship between Genetic and Environmental factors on Human Diseases Gene：a D

8、NA fragment coding for a functional peptide/protein or a RNA.RNA 1RNA 2RNA 31.1 The concepts of Genetics in MedicineThe Concept of Gene What is Familial Disease What is Congenital Disease What is Inherited Disease or Genetic Disease The relationship between Genetic and Environmental factors on Human

9、 Diseases 1.1 The concepts of Genetics in MedicineThe Concept of Gene What is Familial Disease What is Congenital Disease What is Inherited Disease or Genetic Disease The relationship between Genetic and Environmental factors on Human Diseases 1.1 The concepts of Genetics in MedicineThe Concept of G

10、ene What is Familial Disease What is Congenital Disease What is Inherited Disease or Genetic Disease The relationship between Genetic and Environmental factors on Human Diseases Clinical Case 1A 6-yr old boy came to the clinic;a full term product of regular delivery;fine until most recently with rep

11、eated urinary tract infection, hernias, bladder diverticulae;skeletal abnormalities including occipital exostosesLoose skin, “aged” facesHis cousin and uncle had similar symptoms John, a high school graduate came to the clinic for counseling He has been offered for a full scholarship of hockey He ha

12、s a brother died of sudden cardiac with unknown reasons What should he do?Clinical Case 2Features of medical history that raise genetic concerns Features RiskMultiple affected family membersSingle gene; multifactorial; chromosomalFamily history of known inherited disordersRisk of being affected with

13、 same conditionMatern age 35 yr at deliveryChromosomal abnormality in babyExposure to Rx radiationGonadal mutation or chromosome rearrangementConsanguinity (1st cousin or closer)Infant death or malformation; homozygosity for the same mutant geneHistory of neonatal deaths in the familyRecessive or x-

14、linked disorder; chromosome abnormality1.1 The concepts of Genetics in MedicineGenetics and Medical Sciences The Concept of Gene What is Familial Disease What is Congenital Disease What is Inherited Disease or Genetic Disease The relationship between Genetic and Environmental factors on Human Diseas

15、es The Relationship between Genetic and Environmental Factors on Human DiseasesEvery Disease Has Its Genetic Component (s)Genetic Susceptibility to Viral InfectionVirusGeneConsequenceHIVCCR5 (D32 bp)ResistanceCCR2Delayed progressionCXCL12Delayed progressionMBL2Increased susceptibilityIL10Accelerated

16、 progressionCCL3L1ResistanceHepatitis BTNF-aIncreased persistenceMBL2Increased persistenceVDRDecreased persistenceEBVSH2D1AXLPB19 ParvovirusBlood Group PResistanceSome Historic Landmarks of Genetics in Medicine 1866 Mendel: Genetic inheritance in sweet peas 1910 Morgan: chromosomal basis of linkage1

17、953 Watson & Crick: DNA double helix1959 Lejeune: Down syndrome is trisomy 21 1968 Caspersson: chromosomal banding technique1977 Maxim, Gilbert, Sanger: sequencing1986 Mullis: PCR1990-2003 International: Human Genome Project1.2 The History of Genetics in Medicine Co-fathers of Medical Genetics1957 V

18、ictor McKusick founded the Division of Medical Genetics at Johns Hopkins in the east coastSince 19661.2 The History of Genetics in Medicine Co-fathers of Medical Genetics1957 Motulsky founded the Division of Medical Genetics at U Washington in Seattle, west coast- trained many well known medical gen

19、eticists including Joseph Goldstein (Nobel Price winner)1.2 The History of Genetics in Medicine 1.4.5 Post Human Genome ProjectGenetic Database 1.4.5 Post Human Genome ProjectGenetic Database OMIM Statistics for March 2, 2010 , APOLIPOPROTEIN E; APOEAlternative titles; symbols APOLIPOPROTEIN E, DEFICIENCY OR DEFECT OF, INCLUDEDHYPERLIPOPROTEINEMIA, TYPE III, INCLUDEDDYSBETALIPOPROTEINEMIA DUE TO DEFECT IN APOLIPOPROTEIN E-d, INCLUDEDFAMI