Medical Genetics
01
医学遗传学绪论
introduction to medical
Genetics
Medical Genetics
• Arrangement
• Introduction
• Medical Genetics
• Genetic disease
Medical Genetics
Arrangement
Teacher:
Liu Wen PhD associate prof
(liuwen@shmu.edu.cn)
Liu Xiaoyu PhD assistant Prof
(liubio@163.com)
Alexander Endler PhD
Medical Genetics
• 1.5 credits
• Lecture:2 classes/week (9 weeks)
• Lab:4 classes/week (4 weeks)
Medical Genetics
Lectures
Week
Date
Day
Course
Content
Teacher
10
11.11
Thu
3-4
Medical Genetics & Genetic disease
11
11.18
Thu
3-4
Single Gene Disorder
12
11.25
Thu
3-4
Polygene Disorder
13
12.2
Thu
3-4
Chromosomal Disease
Alexander Endler
14
12.9
Thu
3-4
Mitochondrial Disease
Liu Wen
15
12.16
Thu
3-4
Genetics and Cancer
Liu Wen
16
12.23
Thu
3-4
17
12.30
Thu
3-4
18
1.7
Thu
3-4
Liu Wen
Alexander Endler
Liu Wen
Birth defect
Classroom：1402
Liu Wen
Liu Wen
Students presentation
Exam
Liu Wen
Medical Genetics
Lab training
Week
Date
11
11.19
Fri
5-8
Preparation of chromosome samples
Liu Xiaoyu
12
11.26
Fri
5-8
G banding & samples of chromosome diseases
Liu Xiaoyu
14
12.10
Fri
5-8
Extraction of Genomic DNA
Liu Xiaoyu
15
12.17
Fri
5-8
Detection of gene mutation by PCR
Liu Xiaoyu
Lab：13-214
Day
Course
Content
Teacher
Medical Genetics
• Text book
• Reference
Thompson & Thompson Genetics in Medicine, 7th
Principles of Medical Genetics (Williams & Wikins)
Medical Genetics
Exam:
Exam 40%
Presentation 30%
Lab report 20%
Homework 10％
Medical Genetics
Introduction
46,XY karyotype
Medical Genetics
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.
Medical Genetics
androgen insensitivity syndrome， AIS
（雄激素不敏感综合征） XR
46,XY karyotype
retained testis
Medical Genetics
Introduction
•Mechanism
47,XXY (extra chromosome )
Klinefelter sydrome
mania ??
Medical Genetics
Introduction-Disease and Genetics
A. Disease caused by (or related
to) environmental stress.
SARS
Bird Flu
H1N1 Flu
Medical Genetics
Introduction-Disease and Genetics
Down syndrome
Many of the common physical features
Low IQ
B. Disease caused by (or related to)
genetic factors.
Medical Genetics
Medical Genetics
Introduction-Disease and Genetics
Duchenne muscular dystrophy
caused by a gene mutation
Medical Genetics
Medical Genetics
Introduction-Disease and Genetics
connate rachitis
Conjoined Twins
C. diseases caused by the combined
action of gene and environment.
Medical Genetics
Genetic Disorders : disorders caused
wholly or partly by genetic factors.
Medical Genetics
What is Medical Genetics?
human genetics
Medical Genetics
What is Medical Genetics?
human genetics:
The science of variation and
heredity in human beings.
Medical Genetics
dominate
dominate
widow peak
Evaginable thumb
dominate
recessive
Hair line of the forehead
dominate
recessive
Tongue rolling
Free/attached ear lobe
Homework
☆ Pedigree：
Medical Genetics
Nov 25th
Medical Genetics
Symbols
Medical Genetics
What is Medical Genetics?
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.
Medical Genetics
What is Medical Genetics?
Medical Genetics
Wilson’s disease
Mechanism of Genetic Disease
Medical Genetics
What is Medical Genetics?
Clinical Genetics
the application to diagnosis and
patient care
Medical Genetics
What is Medical Genetics?
diagnosis
albinism
Sickle cell anemia
Medical Genetics
What is Medical Genetics?
Imagining
Diagnosis
Medical Genetics
harelip
Medical Genetics
What is Medical Genetics?
Molecular
Diagnosis
incision enzyme
Gel electrophoresis
Medical Genetics
What is Medical Genetics?
Prevention
phenylphruvic acid
prenatal diagnosis
PKU/PAH (Phenylalanine hydroxylase)
Medical Genetics
What is Medical Genetics?
Therapy
Consult
Medical Genetics
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.
Medical Genetics
Genetic disease
B. Characteristics of genetic
disorders
1.
2.
3.
4.
5.
congenital
mode of inheritance
population distribution
familial
infectious
Medical Genetics
Genetic disease
B. Characteristics of genetic
disorders
1.
2.
3.
4.
5.
congenital
mode of inheritance
population distribution
familial
infectious
Medical Genetics
Down syndrome
albinism
Medical Genetics
Genetic disease
B. Characteristics of genetic
disorders
1.
2.
3.
4.
5.
congenital
mode of inheritance
population distribution
familial
infectious
Medical Genetics
3 Pedigree of Genetic Disease
Medical Genetics
Genetic disease
B. Characteristics of genetic
disorders
1.
2.
3.
4.
5.
congenital
mode of inheritance
population distribution
familial
infectious
Medical Genetics
x
hemophilia
（Blood clotting，to bleed）
Medical Genetics
Genetic disease
B. Characteristics of genetic
disorders
1.
2.
3.
4.
5.
congenital
mode of inheritance
population distribution
familial
infectious
Medical Genetics
• Family number of DMD
Medical Genetics
Genetic disease
B. Characteristics of genetic
disorders
1.
2.
3.
4.
5.
congenital
mode of inheritance
population distribution
familial
infectious
Medical Genetics
Genetic disease
human prion diseases
genetic and infectious
Neuron ： Vacuolar degeneration
Medical Genetics
• Creutzfeldt－Jakob disease
tribe
Medical Genetics
Genetic disease
C. Classification of Genetic Disorders
1.
2.
3.
4.
5.
single-gene disorders
chromosome disorders
multifactorial disorders
somatic cell genetic disorders
mitochondrial disorders
Medical Genetics
Genetic disease
C. Classification of Genetic Disorders
1.
2.
3.
4.
5.
single-gene disorders
chromosome disorders
multifactorial disorders
somatic cell genetic disorders
mitochondrial disorders
Medical Genetics
Genetic disease
Single-gene disorders result
when a mutation causes the protein
product of a single gene to be
altered or missing.
Medical Genetics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
16p13.3p13.12
-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
Medical Genetics
Genetic disease
C. Classification of Genetic Disorders
1.
2.
3.
4.
5.
single-gene disorders
chromosome disorders
multifactorial disorders
somatic cell genetic disorders
mitochondrial disorders
Medical Genetics
In chromosome disorders, entire
chromosomes, or large segments of
them, are missing, duplicated, or
otherwise altered.
Medical Genetics
Medical Genetics
Patau syndrome
Trisomy 13 -- the presence of an
extra (third) chromosome 13 in all of
the cells.
Medical Genetics
Symptoms
• Physical characteristics
• Organ defects
• Mental retardation
Medical Genetics
physical characteristics
small eyes
cleft lip,cleft palate
low-set ears
Medical Genetics
physical characteristics
rocker foot
Medical Genetics
Organ defects
• heart defects
• spinal defects
Medical Genetics
• abnormal genitalia
• gastrointestinal hernias
• polycystic kidney disease
Medical Genetics
mental retardation
• Incomplete brain development
• Low IQ
Medical Genetics
 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
Medical Genetics
Diagnosis &Treatment
• Diagnosis: chromosome analysis
• NO TREATMENT
Medical Genetics
Genetic disease
C. Classification of Genetic Disorders
1.
2.
3.
4.
5.
single-gene disorders
chromosome disorders
multifactorial disorders
somatic cell genetic disorders
mitochondrial disorders
Medical Genetics
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.
Medical Genetics
Genetic disease
Multifactorial disorders result
from mutations in multiple genes,
often coupled with environmental
causes.
Medical Genetics
Genetic disease
C. Classification of Genetic Disorders
1.
2.
3.
4.
5.
single-gene disorders
chromosome disorders
multifactorial disorders
somatic cell genetic disorders
mitochondrial disorders
Medical Genetics
Genetic disease
Somatic cell genetic diseases:
result from the altered genetic
materials in somatic cells.
Medical Genetics
Medical Genetics
Genetic disease
C. Classification of Genetic Disorders
1.
2.
3.
4.
5.
single-gene disorders
chromosome disorders
multifactorial disorders
somatic cell genetic disorders
mitochondrial disorders
Medical Genetics
Genetic disease
Mitochondrial genetic diseases:
Due to the mutation of mitochondrial
DNA.
Medical Genetics
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
mt-3256
tRNALeu(UUR)
PEO
mt-3271
tRNALeu(UUR)
MELAS
mt-3303
tRNALeu(UUR)
心肌病
mt-3260
tRNALeu(UUR)
心肌病/肌病
mt-4269
tRNAIle
心肌病
mt-5730
tRNAAsn
肌病(PEO)
mt-8344
tRNALys
MERRF
mt-8356
tRNALys
MERRF/MELAS
mt-15990
tRNAPro
肌病
mt-8993
A6
NARP/LEIGH
mt-11778
ND4
LHON
mt-4160
ND1
LHON
mt-3460
ND1
LHON
mt-7444
COX1
LHON
mt-14484
ND6
LHON
mt-15257
Cyt6
LHON
Medical Genetics
The End