2. Medical genetics
Medical genetics is one of the most rapidly advancing fields of medicine, and molecular genetics is now integral to all aspects of biomedical science.
Every physician who practices in the 21st century must have an in-depth knowledge of the principles of human genetics and their application to a wide variety of clinical problems.

3. What is a genetic disorder?
A genetic disorder is a disease or defect that is inherited.
Genetic disorders are not always noticeable at birth.

4. Genetic disorders are inherited in one of three ways:
From one generation to the next
When each parent is the carrier of a genetic disorder. (These parents do not have the disorder, but can pass the genes on to their children.)
Because of a change in the genetic information being passed on.

5. What is a birth defect?
A birth defect is an abnormality present at birth.
Not all birth defects are inherited. Some birth defects may result from….

6. Classification of Genetic Diseases
Single gene mendelian medical disorders
Chromosomal disorders
Multifactorial inheritance
Mitochondria inheritance
Somatic mutation

9. Euchromatin and Heterochromatin
Chromosomes may be identified by regions that stain in a particular manner when treated with various chemicals.
Several different chemical techniques are used to identify certain chromosomal regions by staining then so that they form chromosomal bands.
For example, darker bands are generally found near the centromeres or on the ends (telomeres) of the chromosome, while other regions do not stain as strongly.
The position of the dark-staining are heterochromatic region or heterochromatin.
Light staining are euchromatic region or euchromatin.

10. Heterochromatin is classified into two groups: (i) Constitutive and (ii) Facultative.
Constitutive heterochromatin remains permanently in the heterochromatic stage, i.e., it does not revert to the euchromatic stage.
In contrast, facultative heterochromatin consists of euchromatin that takes on the staining and compactness characteristics of heterochromatin during some phase of development.

11. Autosomal X-Linked Y-Linked Mitoch ondrial Total 9443 418 48 37 9946
Autosomal
X-Linked
Y-Linked
Mitoch ondrial
Total
* Gene with known sequence
9443
418 48 37
9946
+ Gene with known sequence   and phenotype
353 38
391
# Phenotype description,   molecular basis known
1506
137 2 27
1672
% Mendelian phenotype or locus,   molecular basis unknown
1303
132 4
1439
Other, mainly phenotypes with suspected mendelian basis
2166
154
2322
14771
879 56 64
15770

12. OMIM Statistics for September 24, 2007 Number of Entries
Autosomal
X-Linked
Y-Linked
Mitocho
ndrial
Total
Gene with known sequence
11222
522 48 37
11829
Gene with known sequence   and phenotype
352 30
382
Phenotype description,   molecular basis known
1957
184 2 26
2169
Mendelian phenotype or locus,   molecular basis unknown
1464
130 4
1598
Other, mainly phenotypes with suspected mendelian basis
1976
142
2120
16971
1008 56 63
18098

13. Total number of loci: 9171 Chr. Loci 1 870 2 568 3 491 4 348 5 435 6
Synopsis of the Human Gene Map
Chr. 
  Loci 1 
870  2 
568  3 
491  4 
348  5 
435  6 
566  7 
421  8 
324 
Chr. 
  Loci 9 
326 
10 
308 
11 
578 
12 
476 
13 
158 
14 
277 
15 
263 
16 
347 
Chr 
  Loc
17 
531 
18 
137 
19 
601 
20 
215 
21 
119 
22 
228  X 
538  Y 
46 

14. OMIM Statistics for October 5, 2009
Autosomal
X-Linked
Y-Linked
Mitochondrial
Total
* Gene with known sequence
12258
602 48 35
12943
+ Gene with known sequence   and phenotype
332 22 2
356
# Phenotype description,   molecular basis known
2365
209 4 26
2604
% Mendelian phenotype or locus,   molecular basis unknown
1644
141 5
1790
Other, mainly phenotypes with suspected mendelian basis
1880
139
2021
18479
1113 59 63
19714

15. Synopsis of the Human Gene Map
Chr. 
  Loci 1 
1194  2 
769  3 
647  4 
463  5 
569  6 
729  7 
534  8 
445 
Chr. 
  Loci 9 
457 
10 
446 
11 
761 
12 
641 
13 
222 
14 
376 
15 
356 
16 
467 
Chr. 
  Loci
17 
705 
18 
173 
19 
766 
20 
304 
21 
141 
22 
301  X 
689  Y 
45 
Total number of loci: 12200

16. Total number of loci: 10432 Synopsis of the Human Gene Map Chr. Loci 1 1 
1009  2 
644  3 
565  4 
388  5 
494  6 
626  7 
460  8 
365 
Chr. 
  Loci 9 
387 
10 
363 
11 
648 
12 
549 
13 
191 
14 
323 
15 
304 
16 
406 
Chr. 
  Loci
17 
611 
18 
149 
19 
675 
20 
257 
21 
133 
22 
262  X 
579  Y 
44 
Total number of loci: 10432

17. What are genetic disorders?
Both environmental and genetic factors have roles in the development of any disease. A genetic disorder is a disease caused by abnormalities in an individual’s genetic material (genome).

18. 1) Single-gene (also called Mendelian or monogenic)
This type is caused by changes or mutations that occur in the DNA sequence of one gene. Genes code for proteins, the molecules that carry out most of the work, perform most life functions, and even make up the majority of cellular structures. When a gene is mutated so that its protein product can no longer carry out its normal function, a disorder can result. There are more than 6,000 known single-gene disorders, which occur in about 1 out of every 200 births. Some examples are cystic fibrosis, sickle cell anemia, Marfan syndrome, Huntington’s disease, and hereditary hemochromatosis.

19. Single-gene (also called Mendelian or monogenic)
This type is caused by changes or mutations that occur in the DNA sequence of one gene
Single-gene disorders are inherited in recognizable patterns:
Autosomal dominant,
Autosomal recessive,
X-linked dominant,
X-linked recessive,

20. MULTIFACTORIAL INHERITANCE
The most common cause of genetic disorders is multifactorial or polygenic inheritance. Traits that are due to the combined effects of multiple genes are polygenic (many genes). When environmental factors also play a role in the development of a trait, the term multifactorial is used to refer to the additive effects of many genetic and environmental factors

21. (2) Multifactorial (also called complex or polygenic)
This type is caused by a combination of environmental factors and mutations in multiple genes. For example, different genes that influence breast cancer susceptibility have been found on chromosomes 6, 11, 13, 14, 15, 17, and 22. Its more complicated nature makes it much more difficult to analyze than single-gene or chromosomal disorders. Some of the most common chronic disorders are multifactorial disorders. Examples include heart disease, high blood pressure, Alzheimer’s disease, arthritis, diabetes, cancer, and obesity. Multifactorial inheritance also is associated with heritable traits such as fingerprint patterns, height, eye color, and skin color.

22. (3) Chromosomal
Chromosomes, distinct structures made up of DNA and protein, are located in the nucleus of each cell. Because chromosomes are carriers of genetic material, such abnormalities in chromosome structure as missing or extra copies or gross breaks and rejoinings (translocations), can result in disease. Some types of major chromosomal abnormalities can be detected by microscopic examination. Down syndrome or trisomy 21 is a common disorder that occurs when a person has three copies of chromosome 21.

23. (4) Mitochondrial
This relatively rare type of genetic disorder is caused by mutations in the nonchromosomal DNA of mitochondria. Mitochondria are small round or rod-like organelles that are involved in cellular respiration and found in the cytoplasm of plant and animal cells. Each mitochondrion may contain 5 to 10 circular pieces of DNA.

25. NONTRADITIONAL PATTERNS OF INHERITANCE
Mosaicism refers to the presence of two or more distinct cell lines This was first recognized in chromosomal disorders
A newer concept is mosaicism for a gene abnormality
Imprinting refers to modification of the gene as it is transmitted through the father or the mother
Uniparental disomy (UPD) refers to a pair of chromosomes being inherited from one parent
There are a few rare conditions due to abnormalities of mitochondrial DNA (mtDNA).
Triplet repeat, unstable mutations: A triplet repeat is an unusual type of mutation in which a triplet of nucleotides increases in number within a gene

28. Punnett square illustrating a cross between HH and hh homozygote parents.

29. Punnett square illustrating a cross between two Hh heterozygotes.

30. Fig. 11.4, Mendel’s 7 garden pea characters.

31. Dihybrid cross: F1 generation

32. Dihybrid cross: F2 generation Ratio: 9:3:3:1

33. Trihybrid crosses:
Involve three independently assorting character pairs.
Results:
64 combinations of 8 different gametes
27 different genotypes
8 different phenotypes (2 x 2 x 2)
Predicted ratio of phenotypes = 27:9:9:9:3:3:31

34. Summary of Mendel’s Principles:
Mendel’s Principle of Uniformity in F1:
F1 offspring of a monohybrid cross of true-breeding strains resemble only one of the parents.
Why? Smooth seeds (allele S) are completely dominant to wrinkled seeds (allele s).
Mendel’s Principle of Segregation:
Recessive characters masked in the F1 progeny of two true-breeding strains, reappear in a specific proportion of the F2 progeny.
Two members of a gene pair segregate (separate) from each other during the formation of gametes. Inheritance is particulate, not blending as previously believed.
Mendel’s Principle of Independent Assortment:
Alleles for different traits assort independently of one another.
Genes on different chromosomes behave independently in gamete production.

35. Rediscovery of Mendel’s Principles:
William Bateson (1902)-experiments with fowl first demonstrated that Mendel’s principles applied to animals.
Bateson argued that mutation (not selection) was the most important force shaping variation in plants and animals.
William Bateson also coined the terms:
Genetics
Zygote F1 F2
Allelemorph ( allele)
Reginald Punnett and William Bateson

41. Thank you for your attention