Galala University Fall 2024 BMS141 Lecture 3 Mendelian Inheritance PDF

F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4  BMS141, Lecture #3 Genetics Mendelian Inheritance Ola Ali Khalifa, MD, PhD Professor and Consultant of Medical Genetics Medical Biochemistry & Molecular Biology Section Dept. of B...

F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4  BMS141, Lecture #3 Genetics Mendelian Inheritance Ola Ali Khalifa, MD, PhD Professor and Consultant of Medical Genetics Medical Biochemistry & Molecular Biology Section Dept. of Basic Medical Sciences 2 Intended Learning Outcomes By the end of this Lecture, you should be able to: ▪ Recall some important genetic terms ▪ Compare and contrast the characteristics and outcomes of autosomal, sex-linked, dominant, and recessive modes of inheritance ▪ Calculate the probability of all genotypic and phenotypic outcomes of a trait based on parental genotype and mode of inheritance ▪ Define penetrance and expressivity  Genetic terms Allele ▪ Alternative forms of a gene found at the same locus on homologous chromosomes. ▪ Dominant and recessive.  Genetic terms Homologus chromosome: Chromosome that pair during meiosis and contain identical loci. Genotype: Genetic constitution of an individual. Phenotype: Observable physical manifestations of a genotype.  Genetic terms Homozygote: Genotype consisting of two (2)identical alleles of a particular gene. It may be normal or abnormal. Heterozygote: Genotype consisting of two (2) different alleles for the same gene. Compound heterozygote: Genotype consisting of two different mutant alleles at a particular gene locus.  Genetic terms Pedigree: A diagram of a family history indicating the family members, their relationship to the proband, and their respect to a particular hereditary condition.  Modes of Inheritance Mendelian (Traditional) inheritance. Non Mendelian (Non-traditional) inheritance. Multifactorial inheritance.  Mendelian Inheritance The patterns of inheritance: Whether the chromosomal location of the gene locus is on an autosome, on a sex chromosome. Whether the phenotype is dominant or recessive. 1. Autosomal Dominant (AD)Inheritance Characteristics: One mutated copy of a gene is sufficient (enough)to cause (manifest) the condition. The phenotype usually appear in every generation. Males and females are usually affected equally. There is male to male transmission. Each affected person usually has one affected parent. An affected individual has a 50% (1 in 2) chance of having a child affected by the disorder. AD inheritance AD inheritance: examples ▪ Achondroplasia. ▪ Marfan syndrome. ▪ Osteogenesis imperfecta (AD type) Achondroplasia  AD inheritance: Concepts ❖Penetrance The proportion of individuals with a particular genotype that express the same phenotype. Penetrance is a proportion that ranges between 0 and 1 (or 0 and 100%). Complete penetrance - When 100% of mutant individuals express the phenotype Incomplete /reduced penetrance - If some of mutant individuals do not express the phenotype  AD inheritance: Concepts ❖Variable Expressivity: The severity of conditions varies between different affected individuals carrying the same gene. Achondroplasia If a normal stature parents having a child with Achondroplasia ? New mutation De novo mutation  2. Autosomal Recessive (AR)Inheritance Characteristics: Two mutated copies of a gene are necessary to cause the condition (homozygous ). Males and females are usually affected equally. Both parents are unaffected carriers (with one mutant gene copy and one normal gene copy) With each pregnancy ,carrier couples have a 25% risk of having an affected child,50% risk of having a child who is a carrier, and 25% chance of having a normal child. AR inheritance AR inheritance: examples B thalassemia. Cystic fibrosis B thalassemia 3. X-Linked dominant (XLD) Inheritance Characteristics: Both males and females express the disease state if a gene mutation is present. The risk of transmitting the disorder, however, differs based on the sex of the individual: o Affected males cannot transmit the condition to their sons but all of their daughters will be affected. o Affected females have a 50% chance with each pregnancy of having an affected child (male or female) XLD inheritance XLD inheritance: examples X-linked hypophosphatemic rickets 4. X-Linked Recessive (XLR) Inheritance Characteristics: Clinical phenotype are always expressed in males but are usually not expressed or rarely expressed in females. One mutant copy of a gene on the X chromosome is sufficient to manifest the condition in males. No male-to-male transmission(i.e. fathers to sons) 4. X-Linked Recessive (XLR) Inheritance Characteristics: Unaffected males do not transmit the disorder. The sons of affected male with an XLR disorder will not be affected. All the daughters of affected male will carry one copy of the mutated gene (heterozygous carrier). 4. X-Linked Recessive (XLR) Inheritance ❑ A woman who is a carrier (unaffected) of an XLR ❖ 50% chance of having sons who are affected. ❖ 50% chance of having daughters who are carriers. XLR inheritance XLR inheritance: examples Duchenne muscular dystrophy  5. Y-Linked Inheritance Characteristics: Y-Linked disorders, also called holandric inheritance. Y-Linked disorders in humans can only be passed from men to their sons.  4. Y-Linked Inheritance Characteristics: Only males are affected, and every son of an affected male is affected. Disorders associated with Y-Linked inheritance are relatively few. 27