Introduction
Medical Genetics
Principles of Medical Genetics,2nd Edition
by TD,Gelehrter,FS,Collins and D,Ginsburg
Instant Notes in Genetics,
by PC,Winter,GI,Hickey and HL,Fletcher
Instant Notes in Molecular Biology,
by PC,Turner,AG,McLennan
Mendelian Inheritance in Man (MIM),
by VA,McKusick
Medical Genetics is the application
of genetics to medical practice.
Medical Genetics
Genetic diseases are the diseases
which are due to altered genetic
materials (genes or chromosomes).
Nature and Nurture
321 4
Several Misunderstand
,Familial disease” is genetic disease
,Congenital disease” is genetic disease
Major Types of Genetic Diseases
Monogenic Disease
Polygenic Disease
Chromosome Disease
Somatic Cell Genetic Diseases
the Hazard of Genetic Disease
15 million neonates
1.3% birth defect &
congenital malformation
70%～ 80% (130~150 thousands)
relate to genetic factor
the Hazard of Genetic Disease
15 million neonates
15% spontaneous abortion
70%~80% (130~150 thousands)
relate to genetic factor
the Hazard of Genetic Disease
15 million neonates
50% (1.12 million) relate to
chromosomal aberration
In the crowd,monogenic disease 3%~5%
polygenic disease 15%~20%
chromosome disease 1%
The first or the second in the death reason:
Malignant tumor (somatic cell genetic disease)
2.2% mental retardation
more than 1/3 relate to genetic factor
the Hazard of Genetic Disease
the Hazard of Genetic Disease
Carrier
Genetic load,the average number of
deleterious mutations per individual
in a population.
1865,Mendel G
A Brief History of Genetics
—— Experiments in Plant Hybridization
1865,Mendel G
A Brief History of Genetics
—— hereditary factor,A a
1909,Johannson —— gene
1957,Benzer —— cistron
1977,Sanger —— overlapping gene
1978,Gilbert —— split gene
—— Experiments in Plant Hybridization
1865,Mendel G
A Brief History of Genetics
1865,Galton F
—— Hereditary Talent and Character
1900,Landsteiner K —— ABO
1924,Bernstein F —— multiple alleles
1908,Hardy-Weinberg law
1909,Nilsson-Ehle H —— multifactorial inheritance
1902,Garrod AE —— inborn errors of metabolism
1941,Beadle GW & Tatum EL
Biochemical Genetics
1949,Pauling L
1956,Ingram VM ——?6Glu?Val
1902,Garrod AE
—— the incidence of alkaptonuria:
a study in clinical individuality
—— the One Gene - One Enzyme Theory
—— sickle cell disease; molecular disease
1910,Morgan TH —— Theory of Gene (1926)
Cytogenetics
1923,Painter TS —— 2n = 48; XX,XY
1952,Hsu TC —— hypotonic shock
1956,Tjio JH —— 2n = 46
1959,Lejune J —— Down’s (＋ 21)
Ford CE —— Turner (XO)
Jacob PA —— Klinefelter (XXY)
1969,Pardue ML —— in site hybridization,ISH
Cytogenetics
1971,Seabright M —— G band
1975,Yunis JJ —— Microcytogenetics
1986,Penkel D —— FISH
1960,Denver system
1961,Lyon M —— Lyon hypothesis
1970,Caspersson T —— banding pattern
1944,Avery OT,et al —— DNA
Molecular Genetics
Avery OT MacLeod CM McCarty M
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
Molecular Genetics
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
The Nobel Prize in Physiology or Medicine 1965
"for their discoveries concerning genetic control of
enzyme and virus synthesis"
Jacob F Monod J
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1967,Holley RW,et al —— genetic code
The Nobel Prize in Physiology or Medicine 1968
"for their interpretation of the genetic code and
its function in protein synthesis"
Holley RW Khorana HG Nirenberg MW
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1967,Holley RW,et al —— genetic code
1968,Arber W,et al —— restriction endonucleases
The Nobel Prize in Physiology or Medicine 1978
Arber W Nathans D Smith H
"for the discovery of restriction enzymes and their
application to problems of molecular genetics"
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1967,Holley RW,et al —— genetic code
1968,Arber W,et al —— restriction endonucleases
1970,Baltimore D,et al —— reverse transcriptase
The Nobel Prize in Physiology or Medicine 1975
Baltimore D Temin HM
"for their discoveries concerning the interaction between
tumour viruses and the genetic material of the cell"
1977,Sanger F —— dideoxy sequencing
Molecular Genetics
The Nobel Prize in Chemistry 1980
Sanger F
"for their contributions concerning the deter-
mination of base sequences in nucleic acids"
1977,Sanger F —— dideoxy sequencing
1985,Mullis K —— polymerase chain reaction
Molecular Genetics
The Nobel Prize in Chemistry 1993
Mullis F
"for his invention of the polymerase chain
reaction (PCR) method"
1977,Sanger F —— dideoxy sequencing
1985,Mullis K —— polymerase chain reaction
Molecular Genetics
1989,Orita M —— PCR-SSCP
1979,Kan YW —— gene diagnosis (RFLP)
1986,Woo LC —— gene diagnosis (ASO)
1991,Anderson WF —— gene therapy (ADA)
1990,human genome project (HGP)
1908,Hardy-Weinberg law
Population Genetics
1954,Neel JV,et al —— epidemiologic genetics
Human Genome Diversity
These disorders are due to single
mutant genes (major gene) with a large
effect on the patient's health and
inherited in Mendelian fashion.
Single Gene Disorder
Single Gene Disorder
Autosomal dominant diseases (AD)
Autosomal recessive diseases (AR)
X-linked dominant diseases (XD)
X-linked recessive diseases (XR)
Y-linked diseases
Mitochondrial disorder
OMIM Statistics for April 26,2004
Autosomal 14330
X-linked 856
Y-linked 48
Mitochondrial 60
15294
http://www.ncbi.nlm.nih.gov/Omim/mimstats.html
Back
Polygenic Disease
Back
Multifactorial disease,MF
Result from a combination of multiple
genetic and environmental factors,Each of
these genes may have a relatively minor
effect (minor gene) and their effects are
additive.
Chromosome Disease
Back
These diseases are due to the
chromosomal aberration,chromosome
numerical abnormality and chromosome
structural aberration.
Syndrome
Somatic Cell Genetic Disease
Tumor & congenital malformation
Result from the altered genetic
materials in somatic cells.
Back
Medical Genetics
Principles of Medical Genetics,2nd Edition
by TD,Gelehrter,FS,Collins and D,Ginsburg
Instant Notes in Genetics,
by PC,Winter,GI,Hickey and HL,Fletcher
Instant Notes in Molecular Biology,
by PC,Turner,AG,McLennan
Mendelian Inheritance in Man (MIM),
by VA,McKusick
Medical Genetics is the application
of genetics to medical practice.
Medical Genetics
Genetic diseases are the diseases
which are due to altered genetic
materials (genes or chromosomes).
Nature and Nurture
321 4
Several Misunderstand
,Familial disease” is genetic disease
,Congenital disease” is genetic disease
Major Types of Genetic Diseases
Monogenic Disease
Polygenic Disease
Chromosome Disease
Somatic Cell Genetic Diseases
the Hazard of Genetic Disease
15 million neonates
1.3% birth defect &
congenital malformation
70%～ 80% (130~150 thousands)
relate to genetic factor
the Hazard of Genetic Disease
15 million neonates
15% spontaneous abortion
70%~80% (130~150 thousands)
relate to genetic factor
the Hazard of Genetic Disease
15 million neonates
50% (1.12 million) relate to
chromosomal aberration
In the crowd,monogenic disease 3%~5%
polygenic disease 15%~20%
chromosome disease 1%
The first or the second in the death reason:
Malignant tumor (somatic cell genetic disease)
2.2% mental retardation
more than 1/3 relate to genetic factor
the Hazard of Genetic Disease
the Hazard of Genetic Disease
Carrier
Genetic load,the average number of
deleterious mutations per individual
in a population.
1865,Mendel G
A Brief History of Genetics
—— Experiments in Plant Hybridization
1865,Mendel G
A Brief History of Genetics
—— hereditary factor,A a
1909,Johannson —— gene
1957,Benzer —— cistron
1977,Sanger —— overlapping gene
1978,Gilbert —— split gene
—— Experiments in Plant Hybridization
1865,Mendel G
A Brief History of Genetics
1865,Galton F
—— Hereditary Talent and Character
1900,Landsteiner K —— ABO
1924,Bernstein F —— multiple alleles
1908,Hardy-Weinberg law
1909,Nilsson-Ehle H —— multifactorial inheritance
1902,Garrod AE —— inborn errors of metabolism
1941,Beadle GW & Tatum EL
Biochemical Genetics
1949,Pauling L
1956,Ingram VM ——?6Glu?Val
1902,Garrod AE
—— the incidence of alkaptonuria:
a study in clinical individuality
—— the One Gene - One Enzyme Theory
—— sickle cell disease; molecular disease
1910,Morgan TH —— Theory of Gene (1926)
Cytogenetics
1923,Painter TS —— 2n = 48; XX,XY
1952,Hsu TC —— hypotonic shock
1956,Tjio JH —— 2n = 46
1959,Lejune J —— Down’s (＋ 21)
Ford CE —— Turner (XO)
Jacob PA —— Klinefelter (XXY)
1969,Pardue ML —— in site hybridization,ISH
Cytogenetics
1971,Seabright M —— G band
1975,Yunis JJ —— Microcytogenetics
1986,Penkel D —— FISH
1960,Denver system
1961,Lyon M —— Lyon hypothesis
1970,Caspersson T —— banding pattern
1944,Avery OT,et al —— DNA
Molecular Genetics
Avery OT MacLeod CM McCarty M
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
Molecular Genetics
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
The Nobel Prize in Physiology or Medicine 1965
"for their discoveries concerning genetic control of
enzyme and virus synthesis"
Jacob F Monod J
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1967,Holley RW,et al —— genetic code
The Nobel Prize in Physiology or Medicine 1968
"for their interpretation of the genetic code and
its function in protein synthesis"
Holley RW Khorana HG Nirenberg MW
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1967,Holley RW,et al —— genetic code
1968,Arber W,et al —— restriction endonucleases
The Nobel Prize in Physiology or Medicine 1978
Arber W Nathans D Smith H
"for the discovery of restriction enzymes and their
application to problems of molecular genetics"
1961,Jacob F & Monod J —— lactose operon
Molecular Genetics
1953,Watson JD & Crick FHC
—— DNA double helix structure
1944,Avery OT,et al —— DNA
1967,Holley RW,et al —— genetic code
1968,Arber W,et al —— restriction endonucleases
1970,Baltimore D,et al —— reverse transcriptase
The Nobel Prize in Physiology or Medicine 1975
Baltimore D Temin HM
"for their discoveries concerning the interaction between
tumour viruses and the genetic material of the cell"
1977,Sanger F —— dideoxy sequencing
Molecular Genetics
The Nobel Prize in Chemistry 1980
Sanger F
"for their contributions concerning the deter-
mination of base sequences in nucleic acids"
1977,Sanger F —— dideoxy sequencing
1985,Mullis K —— polymerase chain reaction
Molecular Genetics
The Nobel Prize in Chemistry 1993
Mullis F
"for his invention of the polymerase chain
reaction (PCR) method"
1977,Sanger F —— dideoxy sequencing
1985,Mullis K —— polymerase chain reaction
Molecular Genetics
1989,Orita M —— PCR-SSCP
1979,Kan YW —— gene diagnosis (RFLP)
1986,Woo LC —— gene diagnosis (ASO)
1991,Anderson WF —— gene therapy (ADA)
1990,human genome project (HGP)
1908,Hardy-Weinberg law
Population Genetics
1954,Neel JV,et al —— epidemiologic genetics
Human Genome Diversity
These disorders are due to single
mutant genes (major gene) with a large
effect on the patient's health and
inherited in Mendelian fashion.
Single Gene Disorder
Single Gene Disorder
Autosomal dominant diseases (AD)
Autosomal recessive diseases (AR)
X-linked dominant diseases (XD)
X-linked recessive diseases (XR)
Y-linked diseases
Mitochondrial disorder
OMIM Statistics for April 26,2004
Autosomal 14330
X-linked 856
Y-linked 48
Mitochondrial 60
15294
http://www.ncbi.nlm.nih.gov/Omim/mimstats.html
Back
Polygenic Disease
Back
Multifactorial disease,MF
Result from a combination of multiple
genetic and environmental factors,Each of
these genes may have a relatively minor
effect (minor gene) and their effects are
additive.
Chromosome Disease
Back
These diseases are due to the
chromosomal aberration,chromosome
numerical abnormality and chromosome
structural aberration.
Syndrome
Somatic Cell Genetic Disease
Tumor & congenital malformation
Result from the altered genetic
materials in somatic cells.
Back
