1、Medical GeneticsPresented byPeiqiong LiDept. of Medical Genetics & Cell BiologyGuangzhou Medical UniversityChapter 1 Introduction 1. What is medical genetics ? 2. History of genetics in medicine (自學(xué)) 3. Environment & genetic disorders 4. Characteristics of genetic disorders 5. Methods for genetic re

2、search 1. what is medical genetics ? Medical genetics is a discipline that deals with the diagnosis, treatment, and the management of hereditary disorders. Medical Genetics Disciplines within human & medical genetics human genetics Genetics: variation & heredityClinical geneticsmedical geneticsDisci

3、plines within medical geneticsGenetics: is a science deals with variation and heredity in all living organisms.Human genetics: variation and heredity in human beings.Medical Genetics: deals with the subset of human variation that is relevance to human genetic disorders and medical research.Clinical

4、genetics: the application of genetics in diagnosis & medical care.Cytogenetics: the study of chromosomesMolecular & Biochemical genetics:structure & function of genesPopulation genetics: distribution of genes & how the frequencies of genes & genotypes are maintained or changed. Cancer genetics: the

5、genetic basis of cancer.Clinical genetics: diagnosis & management.Genetic counseling: the provision of information & assistance to the individuals concerned. Introduction to NCBI & OMIM2. History of medical genetics (read after class)Important databases in NCBIAll DatabasesEverythingPubMedOn-line ca

6、talogue of published papersAbstracts or pdf filesOMIMonline mendelian inheritance in man SNPCommon variantsGeneInformation on genesMap ViewerOMIMOnline Mendelian Inheritance in ManVictor A. McKusick, M.D.Genetic Nosology: A systematic arrangement, or classification, of diseases What does NCBI do?Est

7、ablished in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information - all for the better understanding of molecular processes a

8、ffecting human health and disease. All DatabasesNCBI Web Site-PubMedProteinNucleotideStructureGenomeBooksCancerChromosomesConserved Domains3D DomainsGeneGenome ProjectGENSATGEO ProfilesGEO DatasetsHomoloGeneJournalsLocusLinkMeSHOMIAOMIMPMCPopSetProbePubChem BioAssayPubChem CompoundPugChem SubstanceS

9、NPTaxonomyUniGeneUniSTS Surf in the internet for information You can search information for a specificgenetic disease: use key words such as the name OMIM entry number3. environment & genetic disorders Disease caused by (or related to) genetic factors-Duchenne Muscular dystrophy (DMD/BMD)Chromosomal

10、 disordersDisorders caused wholly or partly by genetic factors G6PD deficinency-Glucose-6-phosphate dehydrogenase deficinency PKU- phenylketonuriaDiseases caused by the combined action of gene and environment Cleft lips with/without palate lipsSchizophreniaNeural tube defectsCleft LipCleft lip with

11、cleft palate Disease caused by (or related to) environmental stressbird Influenza, SARS, burn, et al. Genetic factors Environment factorschromosomaldisordersHurt,traffic accident Tuberculosis Bronchial asthma schizophreniaPeptic ulcer diseasecongenital heart disease Diabetes cleft palate hypertensio

12、nneural tube defects 4. Classification of genetic disordersSingle-gene disordersChromosome disordersMultifactorial disordersSomatic cell genetic disordersMitochondrial diseasesA. Single-gene disorders 1) the causing gene located on chromosome 2) frequency is less than 1/500 0.36% pediatric populatio

13、n 6%8% in hospitalized children B. Chromosome disorders: Down Syndrome 1) due to the excess or deficiency one chromosome or chromosome segments2) 7/1000 liveborn(活產(chǎn)) infants .C. Mitochondrial disordersCaused by mutation of mitochondrial DNA: point mutation or deletion.D. Somatic cell genetic disorde

14、rs -cancer Oncogene-point mutation, chromosome translocation, gene amplification, virus induction tumor gene-tumorigenesisE. Multifactorial disorders: genetic+ environmentSchizophreniaType 1 Diabetes mellitusMental retardation Cleft lips with/without palate Behavior disorders 5% pediatric population

15、 60% entire population4. characteristics of genetic disordersVertical transmissionB) The mutation of genetic materialC) inborn4. characteristics of genetic disordersA) Most of the genetic disorders are rareB) Usually to be congenital C) Of familial origin but not true for multifactorial disorders so

16、me disorders are of late onset not every kind of disorders with familial pattern is genetic disorder圖：海豹嬰兒（無肢或短肢畸形）5.Methods for medical genetics researchPopulation screening: a procedure or test in population to identify whether a disease is caused by gene mutation.B. Pedigree AnalysisIf more than

17、one individual in a family is afflicted with a disease, it is a clue that the disease may be inherited. A doctor needs to look at the family history to determine whether the disease is indeed inherited and, if it is, to establish the mode of inheritance. This information can then be used to predict

18、recurrence risk in future generations C. Twin studies Twin studies help disentangle the relative importance of environmental and genetic influences on individual traits and behaviors.Identical, or monozygotic twins (MZ)Fraternal, or dizygotic, twins (DZ)圖：DZ與MZ的胚胎發(fā)育MZDZDZ圖：MZ的性狀終生都很相似圖:一種原發(fā)性的脊柱側(cè)凸的性狀

19、DZMZEthnic differences Assessing genetic contributions to phenotypic differences among racial and ethnic groups.Ethnic groups differ significantly in terms of incidence rates and mortality rates from age-related degenerative diseases including different types of cancer. Black Americans have three ti

20、mes higher risk of esophageal cancer; doubled risk for multiple myeloma, liver, cervical, and stomach cancer; and 50% higher risk for cancers of the oral cavity and pharynx, larynx, lung, prostate, and pancreas. White Americans have higher incidence rates for melanoma, leukemia, lymphoma, and cancers of the endometrium, thyroid, bladder (in males), ovary, testes, and brain