Genetics Patho Objectives PDF

Genetic Alterations\ \ 1. **Explain Mendelian inheritance including, sex-linked inheritance, autosomal dominant\ and autosomal recessive** - Autosomal Dominant - Describes a trait or disorder in which the phenotype is expressed in those who have inherited only 1 copy of the...

Genetic Alterations\ \ 1. **Explain Mendelian inheritance including, sex-linked inheritance, autosomal dominant\ and autosomal recessive** - Autosomal Dominant - Describes a trait or disorder in which the phenotype is expressed in those who have inherited only 1 copy of the particular gene mutation -- a SINGLE copy of the gene will cause the disorder. - Genes on one of the 22 pairs of autosomes (non-sex chromosomes) - 50% chance of inheriting mutation - Seen in GENERATIONS - Autosomal Recessive - Describes a trait or disorder requiring 2 copies of the gene mutation in order to express gene mutation. - 25% chance of inheriting mutation from two carrier parents - Seen in SINGLE GENERATIONAL families - Both parents must be carriers but typically are heterozygous and do not express the mutation themselves - In BOTH dominant and recessive -- both parents are equally able to transmit/inherit the disorder - Sex-Linked Dominant - Dominant trait or disorder caused by a mutation on the X chromosome. - Expressed in heterozygous females and hemizygous males - Heterozygous female -- has two different versions of the gene inherited by each parent - Hemizygous males -- has one affected gene since males only inherit a single X chromosome - Transmission of X-linked DOMINANT gene from an affected male to his children will result in all his daughters being affected (only 1 affected X to give) and none of his sons. - Transmission of an X-linked DOMINANT gene from an affected female to her children will result in 50% chance of children being affected (two XX but one is unaffected) - Sex-Linked Recessive - Recessive disorder caused by mutation on X chromosome. - Expressed by homozygous females (copy of mutation on EACH of their X chromosomes) and hemizygous males (copy of mutation on their single X chromosome) - NOTE: Male to male transmission does not occur and affected males are always related to each other through affected females. **2. Calculate the probability of passing on a genetic disorder to an offspring given the type of inheritance** \- Autosomal dominant -- 50% chance of passing gene to each child \- Autosomal recessive -- If both parents are carriers there is a 25% chance of passing gene. \- X-Linked dominant -- 50% change of passing to children. \- X-Linked recessive -- Carrier mother has 50% chance of passing mutated gene to children (50% of son being affected and 50% chance of daughter being carrier). Fathers will x-linked disorder will always pass this to his daughters but never to his sons. **3. Define heterozygote advantage and give two examples** \- Heterozygous individuals have a higher chance of survival against certain disease AND lacking enough genetic disease compared to a homozygous person. \- Examples are sickle cell trait and cystic fibrosis 4\. **Identify disorders/diseases with a strong familial history** \- CAD, stroke, htn, cancer, diabetes, pulmonary conditions, mental illness **5. List the key components to an accurate family history to determine genetic risks** \- Any diagnosed diseases, family background such as parents being blood relatives, race, basic demographics, medical conditions, reproductive history, patterns of inheritance **6. Identify mutations (ex. BRCA1 and BRCA2 -- not loci and chromosome) and their\ associated genetic disorders (focus on those listed in the lectures)** 1. Hereditary breast and ovarian cancer a. BRCA 1 and BRCA 2 on tumor suppressor gene b. Autosomal dominant manner (only need 1 copy of the gene from either parent) 2. Colorectal cancer c. Tumor suppressor gene, APC i. Autosomal dominant d. Hereditary nonpolyposis colorectal cancer (HNPCC) ii. 4 mismatch repair genes (MSH2, MLH1, MSH6, PMS2) iii. Autosomal dominant **7. Paraphrase how the study of genomics affects healthcare** 1. Potential for early identification of susceptible people 2. Develop target treatments to prevent or ameliorate impact of disease 3. More precise disease prediction **8. Define key terms such as: penetrance, anticipation, and consanguinity, genotype, and phenotype** 1\. Penetrance -- The proportion of individuals with mutation causing a particular disorder who exhibit clinical symptoms of the disorder -- refers to autosomal dominant disorders 2\. Anticipation - Tendency in certain genetic disorders for individuals in successive generations to present at an earlier age with more severe manifestations. Mutations passed from generation to generation have more significant effects. 3\. Consanguinity - Genetic relatedness between individuals descended from at least ONE common ancestor. 4 Genotype - complete set of genetic material 5 Phenotype - Observable physical or biochemical characteristics of the expression of the gene. Clinical presentation of the GENOTYPE **9. Give examples and compare the risks and benefits of using CRISPR and gene editing in humans.** 1\. Benefits -- targeting genetic disease, cancer treatment, organ transplant, disease prevention 2\. Risks -- off target edits, unforeseen consequences, ethical concerns **10. Define epigenetics and describe internal and external influences on genetics** 1\. Epigenetics is layer on top of the DNA consisting with small chemical modifications and impact on how genes work. Changes how genes are controlled and how they are expressed. \- Environment can change your genetics. Epigenetics makes genes "happy again". Places green lights on resistant genes. We want red lights to resistant genes. 2: Internal influences -- hormones, cellular differentiation, developmental stage and age. 3: External influences -- diet, toxins stress, physical activity, social interactions.