1. Lecture 8: Genetics: Heredity Overview Mendel’s laws and Modern Genetic terminology Patterns of inheritance Genetic disease the chromosomal basis of inheritance Prepared by Mayssa Ghannoum

2. Overview  Mendel discovered the basic principles of heredity by breeding garden peas in planned experiments.  A heritable feature that varies among individuals, such as flower color, is called character.  Each variant for a character, such as purple or white color for flowers, is termed a trait.

3. Overview  Hereditary: the passing on of characteristics (traits) from parents to offspring.  Genetics is the study of heredity.

4. Mendel Hereditary Laws  Mendel used garden peas, because they reproduce sexually having two distinct, male and female, sex cells called gametes → and because their traits are easy to isolate and notice → and are available in many varieties, such as purple or white color for flowers.

5. Mendel Hereditary Laws P Generation (true-breeding parents) F 1 Generation (hybrids) F 2 Generation When F 1 hybrid pea plants are allowed to self-pollinate.  Mendel crossed the peas, and fertilization happened (the uniting of male and female gametes).  Then he took the resulted plants seeds and grew them, and he produced offspring carrying different traits than those of the parent plants.  Cross: combining gametes from parents with different traits.

6.  Then he discovered different laws and rules that explain factors affecting heredity.

7. Mendel Law and Rules 1. Rule of Unit Factors Each organism has two alleles for each trait → Genes: located on chromosomes, they control how an organism develops. → Alleles: different forms of the same gene..

8. Mendel Law and Rules 2. Rule of Dominance → The trait that is observed in the offspring is the dominant trait (abbreviated in an uppercase letters). → The trait that disappears in the offspring is the recessive trait (abbreviated in an lowercase letters). 3. Law of Segregation → The two alleles for a trait must separate when gametes are formed. → A parent randomly passes only one allele for each trait to each offspring. Law of Independent Assortment 4. Law of Independent Assortment: → The genes for different traits are inherited independently of each other.

9. Phenotype & Genotype: Phenotype & Genotype: → → Phenotype: the way an organism looks (such as red hair or brown hair) → → Genotype: the gene combination of an organism such as AA or Aa or aa. Dihybrid & Monohybrid: Dihybrid & Monohybrid: → → Dihybrid Cross: crossing parents who differ in two traits (AAEE with aaee) → → Monohybrid Cross: crossing parents who differ in only one trait (AA with aa). Heterozygous & Homozygous: → → Heterozygous: if the two alleles for a trait are different (Aa). → → Homozygous: if the two alleles for a trait are the same (AA or aa).

10. Patterns of Inheritance  The inheritance of characters determined by single gene deviates from simple Mendelian patterns when alleles are not completely dominant or recessive.  We will discuss in the section below these situations about Degrees of Dominance.

11. Degrees of Dominance  Alleles can show different degrees of dominance and recessiveness in relation to each other. a. Complete dominance In Mendel’s classic pea crosses, the F1 offspring always looked like one of the two paternal varieties because one allele in a pair showed complete dominance over the other. In such situations, the phenotypes of the heterozygote and the dominant homozygote are the same.

12. Degrees of Dominance b. Incomplete dominance For some genes, neither allele is completely dominant, and the F1 hybrids have a phenotype somewhere between those of the two paternal varieties. This phenomenon is called incomplete dominance.

13. Degrees of Dominance c. Co-dominance A condition in which the alleles of a gene pair in a heterozygote are fully expressed thereby resulting in offspring with a phenotype that is neither dominant nor recessive. A typical example showing codominance is the ABO blood group system. For instance, a person having A allele and B allele will have a blood type AB because both the A and B alleles are codominant with each other.

14. Multiple Alleles  Only two alleles exist for the pea character that Mendel studied.  But most genes exist in more than two allelic forms.  The ABO blood groups in human are determined by three alleles of a single gene: I A, I B and i alleles.  A person’s blood group may be one of four types: A, B, AB, O.  These letters refer to two carbohydrates A and B that might be present on the surface of red blood cells.

15. Multiple Alleles  A person’s blood cells may have carbohydrate A (type A blood), carbohydrate B (type B blood), both (type AB blood), or neither (type O blood).  Matching compatible blood groups is critical for safe blood transfusions.

16. Epistasis  In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus.  Example: In mice and many mammals, black coat color is dominant to brown. Let’s designate B and b as the two alleles for this character. For a mouse to have brown fur, its genotype must be bb.  But there is a second gene that determines whether or not pigment will be deposited in the hair.

17. Epistasis  The dominant allele, symbolized by C (for color), results in the deposition of either black or brown pigment, depending on the genotype at the first locus. If the mouse is homozygous recessive for the second locus (cc), then the coat is albino, regardless of the genotype at the black/brown locus.  In this case the gene for pigment deposition (C/c) is said to be epistatic to the gene that codes for black or brown pigment (B/b).

18. Epistasis Illustration of the genotypes and phenotypes predicted for offspring of matings between two black mice of genotype BbCc. The C/c gene, which is epistatic to the B/b gene coding for hair pigment, controls whether or not pigment of any color will be deposited in the hair.

19. Polygenic inheritance  Polygenic inheritance occurs when one phenotypic character is controlled by two or more genes.  These characters are called quantitative characters.  Examples of human polygenic inheritance are height, skin color, eye color and weight.  There is an evidence, that skin pigmentation in humans is controlled by at least three separately inherited genes.

20. Pedigree Analysis  Pedigree: A diagram of a family tree showing the occurrence of heritable traits in parents and offspring over multiple generations.  An importance application of a pedigree is to help us calculate the probability that a child will have a particular genotype and phenotype.  The figure below shows a pedigree of a family where we focus on a recessive trait: attached earlobes. F: is for the dominant allele ( free earlobe) f: is for the recessive allele (attached earlobe).

21. Genetic Disorders  A genetic disorder is a genetic problem caused by one or more abnormalities in the genome, especially a condition that is present from birth (congenital). Most genetic disorders are quite rare and affect one person in every several thousands or millions.  Genetic disorders can be classified as:  Recessively inherited Disorders  Dominantly inherited Disorders  Multifactorial Disorders

22. Recessively inherited Disorders  Disorders known to be inherited as simple recessive trait. These disorders range in severity from relatively mild, such as albinism ( lack of pigmentation, which results in susceptibility to skin cancers and vision problems), to life threatening, such as cystic fibrosis.  These disorders shows up only in the homozygous individuals who inherit one recessive allele from each parent. Heterozygotes, phenotypically normal, may transmit the recessive allele to their offspring and thus are called carriers.

23. Cystic Fibrosis  The most common lethal genetic disease in the US.  The normal allele for the defected gene codes for a membrane protein that functions in the transport of chloride ions between certain cells and the extracellular fluid.  These chloride transport channels are defective or absent in the plasma membranes of children who inherit two recessive alleles for cystic fibrosis.  The result is an abnormal high concentration of extracellular chloride, which causes the mucus that coats cells to become thicker and stickier than normal.  The mucus build up in the pancreas, lungs, digestive tract and other organs, leading to multiple effects, including poor absorption of nutrients from intestines, chronic bronchitis..

24. Sickle-Cell Disease  It’s caused by the substitution of a single amino acid in the hemoglobin protein of red blood cells.  When the oxygen content of an affected individual’s blood is low, the sickle-cell hemoglobin molecules aggregate into long rods that deform the red cells into a sickle shape.  Sickled cells may clump and clog small blood vessels often leading to other symptoms throughout the body, including physical weakness, pain, organ damage, and even paralysis.

25. Dominantly Inherited Disorders  Disorders that occur due to dominant alleles, such as achondroplasia, a form of dwarfism that occurs in one of every 25,000 people.  Heterozygous individuals have the dwarf phenotype.  Dominant alleles that cause a lethal disease are much less common than recessive alleles that do so.  All lethal alleles arise by mutations ( changes to DNA) in cells that produce sperm or eggs.

26. Huntington’s Disease  A degenerative disease of the nervous system, is caused by a lethal dominant allele that has no obvious phenotypic effect until the individual is about 35 to 45 years old.  Once the deterioration of the nervous system begins, it is irreversible and inevitably fatal.  Any child born to a parent who has the allele for Huntington’s disease has a 50% chance of inheriting the allele and the disorder.

27. Multifactorial Disorder  The hereditary diseases we have discussed so far are described as simple Mendelian disorders because they result from abnormality of one or both alleles at a single genetic locus.  Many more people are susceptible to diseases that have a multifactorial basis- a genetic component plus a significant environmental influence.  Heart disease, diabetes, cancer, alcoholism, certain mental illnesses such as schizophrenia and many other diseases are multifactorial.

28. Multifactorial Disorder  In many cases of multifactorial diseases, the hereditary component is polygenic.  For example, many genes affect cardiovascular health, making some of us more prone to than others to heart attacks and strokes.  Exercise, a healthful diet, abstinence from smoking, and an ability to handle stressful situations all reduce our risk of heart disease and some types of cancer.

29. The chromosomal basis of inheritance  Description of the chromosomal basis for the transmission of genes from parents to offspring, along with some important exceptions to the standard mode of inheritance.  Chromosomes and genes are both present in pairs in diploid cells; homologous chromosomes separate and alleles segregate during the process of meiosis  Fertilization restores the paired condition for both chromosomes and genes.  Mendelian genes have specific loci along chromosome, and it is the chromosomes that undergo segregation and independent assortment.

30. Inheritance of Sex Linked Genes  In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosome.  In addition to their role as carriers of genes that determine sex, the sex chromosomes especially X chromosomes have genes for many characters unrelated to sex.  A gene located on either sex chromosome is called a sex linked gene.

31. Inheritance of Sex Linked Genes  Females are XX, and males are XY.  Each ovum contains an X chromosome, while a sperm may contain either an X or a Y chromosome.

32. Sex Linked Disorders in humans  Some disorders caused by recessive alleles on the X chromosome in humans: - Color blindness - Hemophilia It’s a sex linked recessive disorder defined by the absence of one or more of the proteins required for blood clotting.

33. Linked genes  Each chromosome has hundreds or thousands of genes.  Genes located on the same chromosome that tend to be inherited together are called linked genes.

34. Genetic Recombination  The production of offspring with combination of traits that differ from those found in either parent.  After genetic recombination there are two types of offspring produced: 1. Parental type (like parents). 2. Recombinant type or Recombinants (not like parents).

35. Abnormal chromosome number  Non disjunction: pairs of homologous chromosomes do not separate during meiosis1 or sister chromatids fail to separate during meiosis2. → As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy.  Aneuploidy results from the fertilization of gametes in which nondisjunction occurred. → Offspring or zygote with this condition have an abnormal number of a particular chromosome. → Zygote (a fertilized egg) is produced from the union of an ovum with a sperm; gametes.

36. Fig. 15.13, nondisjunction Meiosis I Nondisjunction (a) Nondisjunction of homologous chromosomes in meiosis I (b) Nondisjunction of sister chromatids in meiosis II Meiosis II Nondisjunction Gametes Number of chromosomes n + 1 n – 1 nn

37. Types of Aneuploidy A monosomic zygote2n-1One missing chromosome in zygote A trisomic zygote2n+1One extra chromosome in zygote

38. Human Disorders due to Chromosomal Alterations  Down Syndrome (trisomy 21)  it is an aneuploid condition that results from three copies of chromosome 21  Each body cell has total 47 chromosomes.  Affected persons have facial features, short stature, heart defects, susceptible to respiratory infections and mental retardation. Figure 15.16 Down syndrome

39. Alterations of Chromosomal Structures 1. Deletion: when a chromosomal fragment is lost. 2. Duplication: when a fragment of chromosome is repeated. 3. Inversion: chromosomal fragment attaching to the original chromosome but in reverse orientation. 4. Translocation: breakage of a fragment and joining to a non homologous chromosome.

40. Fig. 15.15 Deletion A B C D E F G HA B C E F G H (a) (b) (c) (d) Duplication Inversion Reciprocal translocation A B C D E F G H A B C B C D E F G H A D C B E F G H M N O C D E F G H M N O P Q RA B P Q R