1. Genetics Islamic University College of Nursing

2. Introduction Our understanding of human genetics improved in the few past years. Our understanding of human genetics improved in the few past years. This was occurred after the discovery of the gene map. This was occurred after the discovery of the gene map. Human diseases and the different disorders are influenced by both environmental and genetic factors with varying degrees, for example, Down syndrome is pure genetic disease, Scurvy is pure due to environmental factors. In between combined such as DM, HTN (Multi-factorial). Human diseases and the different disorders are influenced by both environmental and genetic factors with varying degrees, for example, Down syndrome is pure genetic disease, Scurvy is pure due to environmental factors. In between combined such as DM, HTN (Multi-factorial).

3. Human Cell Normal human cell contains 46 (23 pairs) chromosomes, 22 pair autosomes and the 23rd chromosome is sex pair. Normal human cell contains 46 (23 pairs) chromosomes, 22 pair autosomes and the 23rd chromosome is sex pair. XX for the female and XY for the male. XX for the female and XY for the male. Approximately 50,000 genes encoded in the human DNA. (Deoxyriboneuclic Acid) Approximately 50,000 genes encoded in the human DNA. (Deoxyriboneuclic Acid)

4. 46 23 Mitosis Meiosis I Meiosis II Cell Division

5. Spermatogenesis & Oogenesis Gametogenesis in male and female are principally the same but differ in timing of the various stages. Gametogenesis in male and female are principally the same but differ in timing of the various stages. Spermatogenesis begin in the seminefrous tubules around the puberty & continue out life. Spermatogenesis begin in the seminefrous tubules around the puberty & continue out life. Oogenesis begin in the intrauterine life but is arrested in meiosis I, with completion of the cycle when ovulation occurs and continue up to 50 years old. Oogenesis begin in the intrauterine life but is arrested in meiosis I, with completion of the cycle when ovulation occurs and continue up to 50 years old.

6. Sexual Division of Ova and sperm 46 23 Ova Sperm Meiosis I Meiosis II Normal Polar body Abnormal Polar body Abnormal Normal Not contain cytoplasm

7. Duplication of genetic materials ABCDEFABCDEF ABCDEFABCDEF Short arm (P) Long arm (q) Centromere Male chromosomes Female Chromosomes The Same Proteins

8. Preparation for genetic study 1- Separation of WBCs by centrifugation. 2- Cultivate the lymphocytes by adding phytohemagglutinin. 3- Arrest cell division after about 70 hours by adding colchicines to the culture. 4- Release the chromosomes from the nucleus by adding hypotonic saline. 5- Fix and stain.

9. Indications for chromosomal studies 1. Mental retardation. 2. Multiple congenital abnormalities. 3. Recurrent abortion. 4. Infertility. 5. Ambiguous sex. 6. Leukemia. 7. Failure to thrive child. 8. Some syndromes. (turner).

10. Definitions: Gene: describe the hereditary factor that determine the trait or disorder. Gene: describe the hereditary factor that determine the trait or disorder. Locus: is the position at which the structural gene lies. Individuals have 2 alleles at each locus. Locus: is the position at which the structural gene lies. Individuals have 2 alleles at each locus. Homozygous: if the 2 alleles at a single locus are identical. (Recessive) Homozygous: if the 2 alleles at a single locus are identical. (Recessive)

11. Definitions cont … Heterozygous: if the 2 alleles in a single locus are different. (Dominant) Heterozygous: if the 2 alleles in a single locus are different. (Dominant) Dominant: if the condition is manifest with single gene, example heterozygous state. Dominant: if the condition is manifest with single gene, example heterozygous state. Recessive: if the condition is seen only in the homozygous state. Occurred when the two alleles are abnormal. Recessive: if the condition is seen only in the homozygous state. Occurred when the two alleles are abnormal.

12. Autosomal Recessive Recessive: the condition is seen only in the homozygous state. (identical) Recessive: the condition is seen only in the homozygous state. (identical) Occurred when the two alleles are abnormal. Occurred when the two alleles are abnormal. The disorder is more common among consangeous marriage. Siblings have one half of their genes in common, where first cousins have one-eight of their genes in common. The disorder is more common among consangeous marriage. Siblings have one half of their genes in common, where first cousins have one-eight of their genes in common. One third of inherited traits are AR. One third of inherited traits are AR.

13. Criteria of AR disorders 1. Parents are usually healthy. 2. Affected individuals are almost the offspring of heterozygot carrier parents. 3. Percent % to be affected of children if the parents are carriers is 1:4. 4. If both parents are affected all children will be affected. 5. Both sexes are affected equally. 6. It causes mainly enzyme deficiency. 7. Example: Cystic Fibrosis, Galactosomia, Phenlketonurea, Thalassemia, and others.

14. Autosomal Dominant (AD) Dominant means that the disease allele or gene need to be present only in single copy (heterozygot) to result in phenotype. Dominant means that the disease allele or gene need to be present only in single copy (heterozygot) to result in phenotype. The affected individuals posses both the abnormal and normal gene. The affected individuals posses both the abnormal and normal gene. More than half of the inherited traits are autosomal dominant. More than half of the inherited traits are autosomal dominant.

15. Criteria of Autosomal (AD) disorder Disease is transmitted from generation to generation and can be tracked to several generations. Disease is transmitted from generation to generation and can be tracked to several generations. Sporadic cases can occur due to new mutations, it occur more frequently in sever cases in which the chance of survival or reproduction of the affected persons are low. Sporadic cases can occur due to new mutations, it occur more frequently in sever cases in which the chance of survival or reproduction of the affected persons are low. It affect both sexes equally. It affect both sexes equally.

16. Criteria of Autosomal (AD) disorder The risk of transmission to the offspring is 50% they show variability in severity. The risk of transmission to the offspring is 50% they show variability in severity. Anticipation: The severity of the disease tended to increase with each generation. Anticipation: The severity of the disease tended to increase with each generation. An example: Myotonic dystrophy, the grandfather could have cataract only, the mother had myotonia and muscle weakness and the affected child had congenital myotonic dystrophy with developmental delay. An example: Myotonic dystrophy, the grandfather could have cataract only, the mother had myotonia and muscle weakness and the affected child had congenital myotonic dystrophy with developmental delay.

17. Example of AD Achondroplasia. (disease of bone growth cause short structure M. 131, F124, not able to convert cartilage into long bone). Achondroplasia. (disease of bone growth cause short structure M. 131, F124, not able to convert cartilage into long bone). Neurofibromatosis. (NF1)causes skin changes and deformed bones. It usually starts in childhood. Sometimes the symptoms are present at birth. (NF2) causes hearing loss, ringing in the ears, and poor balance. Symptoms often start in the teen years. Neurofibromatosis. (NF1)causes skin changes and deformed bones. It usually starts in childhood. Sometimes the symptoms are present at birth. (NF2) causes hearing loss, ringing in the ears, and poor balance. Symptoms often start in the teen years.

18. Example of AD Polycystic Kidney disease. (ADPKD) is a multi-systemic and progressive disorder characterized by cyst formation and enlargement in the kidney and other organs (eg, liver, pancreas, spleen). Up to 50% of patients with ADPKD require renal replacement therapy by 60 years of age. Polycystic Kidney disease. (ADPKD) is a multi-systemic and progressive disorder characterized by cyst formation and enlargement in the kidney and other organs (eg, liver, pancreas, spleen). Up to 50% of patients with ADPKD require renal replacement therapy by 60 years of age. Retinoblastoma. (is the most common primary ocular malignancy of childhood). Retinoblastoma. (is the most common primary ocular malignancy of childhood). Spherocytosis. is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to fulminant hemolytic anemia Spherocytosis. is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to fulminant hemolytic anemia

19. X-linked diseases Transmitted by heterozygous mother to sons Transmitted by heterozygous mother to sons Daughters - 50% carriers, 50% healthy Daughters - 50% carriers, 50% healthy Sons - 50% diseased, 50% healthy Sons - 50% diseased, 50% healthy Children of diseased father - sons are healthy, all daughters are carriers Children of diseased father - sons are healthy, all daughters are carriers Hemophilia A (defect of Factor VIII) Hemophilia A (defect of Factor VIII) Hemophilia B (defect of Factor IX) Hemophilia B (defect of Factor IX) Muscle dystrophy (Duchen disease) Muscle dystrophy (Duchen disease)

20. Autosomal disorders Trisomy 21 (Down syndrome) Most frequent - 1:700 births; parents have normal karyo-type. Most frequent - 1:700 births; parents have normal karyo-type. Maternal age has a strong influence: 45 y. 1:25 live births Maternal age has a strong influence: 45 y. 1:25 live births Most frequently is abnormality in ovum (ovum is under long-time influence of environment) Most frequently is abnormality in ovum (ovum is under long-time influence of environment)

21.  HEREDITY The passing of traits from parent to offspring.  ALLELE The different forms of a trait that a gene may have. One form of a gene GENOTYPE An organism's genetic makeup. GENOTYPE An organism's genetic makeup. PHENOTYPE PHENOTYPE Outward physical appearance and behavior of an organism. Outward physical appearance and behavior of an organism. TRAIT Ways of looking, thinking, or being. Traits that are genetic are passed down through the genes from parents to offspring. TRAIT Ways of looking, thinking, or being. Traits that are genetic are passed down through the genes from parents to offspring.

24. Autosomal Dominant

26. Autosomal Recessive

28. Sex linked disease