1. Medical Genetics MVI-851 Lecture 1

2. Introduction to Genetics
GENETICS – branch of biology that deals with heredity and variation of organisms.
Chromosomes carry the hereditary information (genes)
Arrangement of nucleotides in DNA
DNA  RNA  Proteins

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

4. What is Medical Genetics?
human genetics

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

6. 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.

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

8. Chromosomes (and genes) occur in pairs Homologous Chromosomes
New combinations of genes occur in sexual reproduction
Fertilization from two parents

9. Genetics terms you need to know:
Gene – a unit of heredity; a section of DNA sequence encoding a single protein
Genome – the entire set of genes in an organism
Alleles – two genes that occupy the same position on homologous chromosomes and that cover the same trait (like ‘flavors’ of a trait).
Locus – a fixed location on a strand of DNA where a gene or one of its alleles is located.

10. Homozygous – having identical genes (one from each parent) for a particular characteristic.
Heterozygous – having two different genes for a particular characteristic.
Dominant – the allele of a gene that masks or suppresses the expression of an alternate allele; the trait appears in the heterozygous condition.
Recessive – an allele that is masked by a dominant allele; does not appear in the heterozygous condition, only in homozygous.

11. Genotype – the genetic makeup of an organisms
Phenotype – the physical appearance
of an organism (Genotype + environment)
Monohybrid cross: a genetic cross involving a single pair of genes (one trait); parents differ by a single trait.
P = Parental generation
F1 = First filial generation; offspring from a genetic cross.
F2 = Second filial generation of a genetic cross

12. albinism What is Medical Genetics? diagnosis
There are three basic types of melanin: eumelanin (Brown n Black), pheomelanin (red), and neuromelanin
Sickle cell anemia-hemoglobin-Beta gene found on chromosome 11

13. What is Medical Genetics?
Molecular
Diagnosis
Physical examination
Personal medical history
Family medical history
Biochemical tests (chromosomal karyotype)
Gel electrophoresis

14. What is Medical Genetics?
Prenatal diagnosis is a way for your doctor to determine, before birth, whether your fetus has a problem such as Down syndrome. Amniocentesis and chorionic villus sampling (CVS) are tests that help find genetic disorders before birth.
Prevention

15. What we can get from chromosomal analysis?

16. What is Medical Genetics?
Therapy
Consult

17. 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.

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

19. Down syndrome (Trisomy 21)
47,XXY (extra chromosome )
Klinefelter sydrome
albinism

20. Genetic disease B. Characteristics of genetic disorders 1. congenital
2. mode of inheritance (XX and XY)
3. population distribution (defective factor VIII, a clotting protein)
4. familial (A high level of the enzyme creatine kinase (CK) can indicate DMD)
5. infectious

21. Genetic disease human prion diseases genetic and infectious Acquired
Genetic (PRNP gene)
Heredity
Sporadic
It’s often estimated that human prion disease cases are 85% sporadic, 15% genetic and < 1% acquired 
Neuron ： Vacuolar degeneration

22. 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.

23. Introduction-Disease and Genetics
A. Disease caused by (or related to) environmental stress.
Bird Flu (HFN1)
SARS
H1N1 Flu

24. Introduction-Disease and Genetics
Down syndrome
Trisomy of chromosome 21
Many of the common physical features
Low IQ

25. 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

26. 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

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

28. 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

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

30. The Philadelphia Chromosome found in patients with Chronic Myeloid Leukemia causes a fusion protein to be made from a combination of genes on chromosomes 9 and 22.

31. Translocation Involved in Burkitt’s Lymphoma

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

33. Symptoms
Physical characteristics
Organ defects
Mental retardation

34. physical characteristics
small eyes
cleft lips and nose
low-set ears

35. physical characteristics
rocker foot

36. Organ defects
heart defects
spinal defects

37. abnormal genitalia
gastrointestinal
polycystic kidney disease

38. mental retardation
Incomplete brain development
Low IQ

39. 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

40. Diagnosis &Treatment
Diagnosis: chromosome analysis

41. Genetic disease C. Classification of Genetic Disorders
1. single-gene disorders
2. chromosome disorders
3. multifactorial disorders (Multifactorial disorders result from mutations in multiple genes, often coupled with environmental causes)
4. somatic cell genetic disorders (result from the altered genetic materials in somatic cells)
5. mitochondrial disorders

42. 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.

43. 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