01 医学遗传学绪论 introduction to medical Genetics

Arrangement Introduction Medical Genetics Genetic disease

Arrangement Teacher: Liu Wen PhD associate prof (liuwen@shmu.edu.cn) Liu Xiaoyu PhD assistant Prof (liubio@163.com) Alexander Endler  PhD

1.5 credits Lecture:2 classes/week (9 weeks) Lab:4 classes/week (4 weeks)

Lectures 10 Thu 3-4 Liu Wen 11 12 13 14 15 16 17 18 Classroom：1402 Week Date Day Course Content Teacher 10 11.11 Thu 3-4 Medical Genetics & Genetic disease Liu Wen 11 11.18 Single Gene Disorder Alexander Endler 12 11.25 Polygene Disorder 13 12.2 Chromosomal Disease 14 12.9 Mitochondrial Disease 15 12.16 Genetics and Cancer 16 12.23 Birth defect 17 12.30 Students presentation 18 1.7 Exam　 Classroom：1402

Lab training Lab：13-214 11 Fri 5-8 12 14 15 Week Date Day Course Content Teacher 11 11.19 Fri 5-8 Preparation of chromosome samples Liu Xiaoyu 12 11.26 G banding & samples of chromosome diseases 14 12.10 Extraction of Genomic DNA 15 12.17 Detection of gene mutation by PCR Lab：13-214

Thompson & Thompson Genetics in Medicine, 7th Text book Reference Thompson & Thompson Genetics in Medicine, 7th Principles of Medical Genetics (Williams & Wikins)

Exam: Exam 40% Presentation 30% Lab report 20% Homework 10％

Introduction First Story 46,XY karyotype

Androgen insensitivity syndrome, AIS Mechanism Caused by mutations of the gene encoding the androgen receptor. symptoms A person with complete androgen insensitivity syndrome (CAIS) has a female external appearance, and suppressed menstruation.

androgen insensitivity syndrome， AIS（雄激素不敏感综合征） XR 46,XY karyotype retained testis

Introduction Second Story Mechanism 47,XXY (extra chromosome ) Klinefelter sydrome mania ??

Introduction-Disease and Genetics A. Disease caused by (or related to) environmental stress. Bird Flu SARS H1N1 Flu

Introduction-Disease and Genetics B. Disease caused by (or related to) genetic factors. Down syndrome Many of the common physical features Low IQ

Introduction-Disease and Genetics Duchenne muscular dystrophy caused by a gene mutation

Introduction-Disease and Genetics connate rachitis Conjoined Twins C. diseases caused by the combined action of gene and environment.

Genetic Disorders : disorders caused wholly or partly by genetic factors.

What is Medical Genetics? human genetics

What is Medical Genetics? human genetics: The science of variation and heredity in human beings.

dominate dominate widow peak Evaginable thumb Hair line of the forehead dominate dominate recessive recessive Free/attached ear lobe Tongue rolling

Homework ☆ Pedigree： Nov 25th

Symbols

What is Medical Genetics? Medical genetics deals with human genetic variation of medical significance. Major recognized areas of specialization are the study of chromosomes, and the structure and function of individual genes.

What is Medical Genetics? Wilson’s disease Mechanism of Genetic Disease

What is Medical Genetics? Clinical Genetics the application to diagnosis and patient care

What is Medical Genetics? diagnosis albinism Sickle cell anemia

What is Medical Genetics? Imagining Diagnosis

harelip

What is Medical Genetics? Molecular Diagnosis incision enzyme Gel electrophoresis

What is Medical Genetics? Prevention phenylphruvic acid prenatal diagnosis PKU/PAH (Phenylalanine hydroxylase)

What is Medical Genetics? Therapy Consult

Genetic disease A. What is genetic disorder? A genetic disorder is a disease that is caused by an abnormality in an individual’s DNA. Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or set of chromosomes.

Genetic disease B. Characteristics of genetic disorders 1. congenital 2. mode of inheritance 3. population distribution 4. familial 5. infectious

Genetic disease B. Characteristics of genetic disorders 1. congenital 2. mode of inheritance 3. population distribution 4. familial 5. infectious

Down syndrome albinism

Genetic disease B. Characteristics of genetic disorders 1. congenital 2. mode of inheritance 3. population distribution 4. familial 5. infectious

3 Pedigree of Genetic Disease

Genetic disease B. Characteristics of genetic disorders 1. congenital 2. mode of inheritance 3. population distribution 4. familial 5. infectious

x hemophilia （Blood clotting，to bleed）

Genetic disease B. Characteristics of genetic disorders 1. congenital 2. mode of inheritance 3. population distribution 4. familial 5. infectious

Family number of DMD

Genetic disease B. Characteristics of genetic disorders 1. congenital 2. mode of inheritance 3. population distribution 4. familial 5. infectious

Genetic disease human prion diseases genetic and infectious Neuron ： Vacuolar degeneration

Creutzfeldt－Jakob disease tribe

Genetic disease C. Classification of Genetic Disorders 1. single-gene disorders 2. chromosome disorders 3. multifactorial disorders 4. somatic cell genetic disorders 5. mitochondrial disorders

Genetic disease C. Classification of Genetic Disorders 1. single-gene disorders 2. chromosome disorders 3. multifactorial disorders 4. somatic cell genetic disorders 5. mitochondrial disorders

Genetic disease Single-gene disorders result when a mutation causes the protein product of a single gene to be altered or missing.

表 一些常染色体显性遗传病举例 疾病中文名称 疾病英文名称 OMIM 染色体定位 家族性高胆固醇血症 表 一些常染色体显性遗传病举例 疾病中文名称 疾病英文名称 OMIM 染色体定位 家族性高胆固醇血症 familial hypercholesterolemia 143890 19p13.2 遗传性出血性毛细血管扩张 hemorrhagic telangiectasia 187300 9q34.1 遗传性球形红细胞症 elliptocytosis 130500 1p36.2-p34 急性间歇性卟淋症 porphyria, acute intermittent 176000 11q23.3 迟发性成骨发育不全症 osteogenesis imperfecta, type I 166200 17q21.31-q22 成年多囊肾病 polycystic kidney disease, adult 173900 16p13.3-p13.12 -珠蛋白生成障碍性贫血 alpha-thalassemias 141800 16pter-p13.3 短指（趾）症A1型 brachydactyly, type A1 112500 2q35-q36 特发性肥大性主动脉瓣下狭窄 supravalvular aortic stenosis 185500 7q11.2 遗传性巨血小板病，肾炎和耳聋 Fechtner syndrome 153640 22q11.2 Noonan综合征 Noonan syndrome 1 163950 12q24.1 神经纤维瘤 neurofibromatosis, type I 162200 17q11.2 结节性脑硬化 tuberous sclerosis 191100 16p13.3，9q34 多发性家族性结肠息肉症 adenomatous polyposis of the colon 175100 5q21-q22 Peutz-Jeghers综合征 Peutz-Jeghers syndrome 175200 19p13.3 Von Willebrand病 Von Willebrand disease 193400 12p13.3 肌强直性营养不良 dystrophia myotonica 1 160900 19q13.2-q13.3

Genetic disease C. Classification of Genetic Disorders 1. single-gene disorders 2. chromosome disorders 3. multifactorial disorders 4. somatic cell genetic disorders 5. mitochondrial disorders

In chromosome disorders, entire chromosomes, or large segments of them, are missing, duplicated, or otherwise altered.

Patau syndrome   Trisomy 13 -- the presence of an extra (third) chromosome 13 in all of the cells.

Symptoms Physical characteristics Organ defects Mental retardation

physical characteristics small eyes cleft lip,cleft palate low-set ears

physical characteristics rocker foot

Organ defects heart defects spinal defects

abnormal genitalia gastrointestinal hernias polycystic kidney disease

mental retardation Incomplete brain development Low IQ

99％do not survive gestation and are spontaneously aborted   99％do not survive gestation and are spontaneously aborted 82-85% do not survive past 1 month of age, 85% do not survive past 1 year of age

Diagnosis &Treatment Diagnosis: chromosome analysis NO TREATMENT

Genetic disease C. Classification of Genetic Disorders 1. single-gene disorders 2. chromosome disorders 3. multifactorial disorders 4. somatic cell genetic disorders 5. mitochondrial disorders

Multiple genes are missing as a result of this deletion, and each may contribute to the symptoms of the disorder. One of the deleted genes known to be involved is TERT (telomerase reverse transcriptase). This gene is important during cell division because it helps to keep the tips of chromosomes (telomeres) in tact.

Genetic disease Multifactorial disorders result from mutations in multiple genes, often coupled with environmental causes.

Genetic disease C. Classification of Genetic Disorders 1. single-gene disorders 2. chromosome disorders 3. multifactorial disorders 4. somatic cell genetic disorders 5. mitochondrial disorders

Genetic disease Somatic cell genetic diseases: result from the altered genetic materials in somatic cells.

Genetic disease C. Classification of Genetic Disorders 1. single-gene disorders 2. chromosome disorders 3. multifactorial disorders 4. somatic cell genetic disorders 5. mitochondrial disorders

Genetic disease Mitochondrial genetic diseases: Due to the mutation of mitochondrial DNA.

一些mtDNA突变相关的疾病 突变 相关基因 表型 mt-3243 tRNALeu(UUR) MELAS、PEO、NIDDM/耳聋 心肌病 mt-3260 心肌病/肌病 mt-4269 tRNAIle mt-5730 tRNAAsn 肌病(PEO) mt-8344 tRNALys MERRF mt-8356 MERRF/MELAS mt-15990 tRNAPro 肌病 mt-8993 A6 NARP/LEIGH mt-11778 ND4 LHON mt-4160 ND1 mt-3460 mt-7444 COX1 mt-14484 ND6 mt-15257 Cyt6

The End