Patterns of Inheritance (Genetics)

Lecture for B.Sc Nursing II Year

1. Mrs bincy varghese Associate professor nursing Unit I (Genetics) Patterns of Inheritance

2. Terminologies Genetics: Study of heredity. Genome: An organism’s complete set of DNA including genes. Genomics: Study of genes, their functions and related techniques.

3. Mendel and Mendelism The principles of Genetics was laid by Gregor Johann Mendel. (Father of Genetics) Born on July 22, 1822 in Heinzendorf , Austria (Czechoslovakia). He conducted experiments on Garden pea plant. He selected 7 pairs of contrasting characters in the Garden pea such as height, shape, texture of seed, flower position and colour. He crossed these varieties of plants.

4. Heterozygous/Hybrids thus obtained formed F1 generation . Plants in F1 generation resembled one of their parents. (Cross between tall (T) and dwarf plants (t) resulted in all Tall plants (T) ). The characteristics expressed in hybrids were called Dominant character.(T) The characteristics not expressed in hybrids were called Recessive character.(t)

5. Plants in F1 generation were allowed to self pollinate. This led to F2 generation . Analysis of F2 generation revealed both types of plants, one expressing dominant character (tall-T) and the other expressing recessive characters (dwarf-t). F2 generation plants expressing recessive characters were self pollinated. This resulted in F3 generation with all the plants expressing recessive character (t).

6. MENDEL’S LAW OF INHERITANCE Law of dominance In heterozygous, the allele which masks the other is referred to as Dominant while the allele that is masked is referred to as Recessive. Dominant alleles are expressed exclusively in a heterozygotes while recessive traits are expressed only if the organism is homozygous for the recessive allele.

7. Law of Segregation This law states that members of gene pair separate and pass to different gametes. (Chromosomes separate into different gametes during meiosis, the two different allele for a particular gene also segregate so that each gamete acquires one of the two alleles.) A diploid organism passes a randomly selected allele for a trait to its offspring such as that the offspring receives one allele from each parent.

8. Law of independent assortment Separate genes for separate traits are passed independently of one another from parents to offsprings during gametogenesis.

9. Mendelian Disorder/Single Gene Disorder They are caused by a single mutant gene. They follow one of three patterns of inheritance: Autosomal Dominant Inheritance Autosomal Recessive Inheritance Sex linked inheritance (X linked dominant and recessive inheritance & Y linked inheritance)

10. Autosomal Dominant Inheritance "Autosomal" means that the gene in question is located on one of Autosomes. "Dominant" means that a single copy of the disease-associated mutation is enough to cause the disease. This is in contrast to a recessive disorder, where two copies of the mutation are needed to cause the disease. Autosomal dominant trait expresses in heterozygous state

11. Characteristics : An affected person has an affected parent. There is 50% chance of dominant trait being transmitted to offsprings from affected parent. (normal and abnormal offsprings in equal proportions) Both males and females are equally affected

12. The trait appears in every generation without skipping. Normal children of an affected person do not transmit the disease. They can have variable expression. Some people have mild or more intense characteristics than others. Some people can have dominant gene copy but not show any signs of the gene.

13. Most common, life threatening, renal disease. Fluid filled cysts develop and enlarge in both kidneys leading to Renal failure. Usually develops in the ages of 30-40, symptoms tends to get worse with time. Treatment includes Antihypertensives and Dialysis (in case of renal failure) E.g. Autosomal Dominant Polycystic Kidney Disease

14. Autosomal Recessive Inheritance The recessive trait only expressed in homozygote state. (To have autosomal recessive disorder, two mutated genes are needed, one from each parent. These disorders are passed on by two carriers) Two carriers have a 25% chance of having an unaffected child with 2 normal genes, 50 % chance of having an unaffected child who is a carrier, 25 % chance of having an affected child with 2 recessive genes.

15. E.g. Sickle Cell Anemia Inherited red blood cell disorder which lacks healthy RBCs to carry oxygen. People with this disorder have atypical Hemoglobin called Hemoglobin-S which can distort the RBC into the shape of sickle or crescent moon. Sign and symptoms: Sickling of RBC (breakdown prematurely and leads to anemia), jaundice, organ damage. No cure, only symptomatic management.

16. Sex linked inheritance The inheritance of a trait (phenotype) that is determined by a gene located on one of the sex chromosomes is called Sex linked inheritance. In mammals, the female is homogametic, with two X chromosomes (XX), while the male is the heterogametic sex, with one X and one Y chromosome (XY). Genes on the X or Y chromosome are called sex-linked . So, sex-linked diseases are carried by sex chromosomes only. In humans it is called X-linked or Y-linked inheritance.

17. The Y chromosome is much shorter and contains many fewer genes. The X chromosome has about 800-900 protein-coding genes with a wide variety of functions, while the Y chromosome has just approx. 200 protein-coding genes. The human Y chromosome plays a key role in determining the sex of a developing embryo. This is mostly due to a gene called SRY (“sex-determining region of Y”) . SRY is found on the Y chromosome and encodes a protein that turns on other genes required for male development.

18. XX embryos don't have SRY, so they develop as female. XY embryos do have SRY, so they develop as male.

19. X LINKED INHERITANCE When a gene is present on the X chromosome, but not on the Y chromosome, it is said to be X-linked . Since a female has two X chromosomes, she will have two copies of each X-linked gene. A male has different genotype possibilities than a female. Since he has only one X chromosome (paired with a Y), he will have only one copy of any X-linked genes. In humans, the alleles for certain conditions (including some forms of color blindness, hemophilia, and muscular dystrophy) are X-linked. These diseases are much more common in men than they are in women due to their X-linked inheritance pattern.

20. E.g. A mother is heterozygous for a disease-causing allele. Women who are heterozygous for disease alleles are said to be carriers, and they usually don't display any symptoms themselves. Sons of these women have a 50% percent chance of getting the disorder, but daughters have little chance of getting the disorder (unless the father also has it), and will instead have a 50% percent chance of being carriers.

21. Recessive X-linked traits appear more often in males than females because, if a male receives a "bad" allele from his mother, he has no chance of getting a "good" allele from his father (who provides a Y) to hide the bad one. Females, on the other hand, will often receive a normal allele from their fathers, preventing the disease allele from being expressed.

22. Hemophilia (X linked Disorder) Hemophilia, a recessive condition in which a person's blood does not clot properly. Hemophilia is caused by a mutation of genes located on the X chromosome that help in blood clot. Since the mother is a carrier, she will pass on the hemophilia allele ( X h ) on to half of her children, both boys and girls. None of the daughters will have hemophilia (zero chance of the disorder). That's because, in order to have the disorder, they must get a ( Xh ) allele from both their mother and their father. The sons get a Y from their father instead of an X, so their only copy of the blood clotting gene comes from their mother. The mother is heterozygous, so half of the sons, on average, will get an ( Xh ) allele and have hemophilia (1/ 2 chance of the disorder).

23. X linked Dominant and Recessive Disorder X linked Dominant Inheritance/ X linked dominance is a mode of genetic inheritance by which a dominant gene is carried on the X chromosomes. Only one copy of allele is sufficient to cause the disorder when inherited from the parent with the disorder. All fathers affected by X linked Dominant Disorder will have affected daughters but not son. However, if the Mother is also affected then sons will have a chance of being affected.

24. List of X linked Dominant Diseases: Alport Syndrome (Characterised by Glomerulonephritis, ESRD and hearing loss, vision changes) Fragile X Syndrome (Characterised by mild-moderate intellectual disability, long and narrow face, large ears, autism, hyperactivity, seizures). Rett’s Syndrome (Brain disorder, problems with language, coordination, repetitive movements, seizures, scoliosis)

25. X linked Recessive Inheritance refers to genetic conditions associated with mutations in genes on the X chromosomes. A male carrying such a mutation will be affected because he carries only one X chromosomes. A female carrying a mutation in one gene with a normal gene on the other X chromosomes is generally unaffected. E.g Red Green Colour Blindness (Person cannot distinguish between shades of red and green. Their visual acuity is normal) Hemophilia

26. Y Linked Inheritance Describes traits that are produced by genes located on the Y chromosome. For a trait to be considered Y linkage, it must exhibit these characteristics: occurs only in males appears in all sons of males who exhibit that trait is absent from daughters of trait carriers The concept of dominant and recessive do not apply to Y linked traits as only one allele is present in males.

27. E.g. Y Chromosome Infertility Y chromosome infertility s a condition that affects the production of sperm and causes male infertility. The affected man’s body may produce no mature sperm cells (Azoospermia), fewer than the usual number of sperms ( oligospermia ) or sperm cells that are abnormally shaped