2.  Understand what are the following: human cell, chromosomes, and genes.  Explain the errors that can occur in Meiosis and Mitosis  Explain the differences between autosomal recessive, autosomal dominant, and X- Linked genetic disorders.  Understand inheritance patterns in single- gene disorders which are seen through geno-imprinting, anticipation, and mitochondrial inheritance  Understand that environmental issues can also cause issues with development

3.  Disease cause by an error in an individuals DNA during fetal development › These errors include…  Errors in Cell Division  Errors in Chromosome Division  Adding or deleting Chromosomes  Mutations within Gene’s or a Single Gene

4.  Two Key Parts: Nucleus and Cytoplasm › Nucleus  Chromosome & DNA organized into Gene’s needed for life › Cytoplasm  Gene in the nucleus are dependent on the cytoplasm › The Nucleus and Cytoplasm need to be working in unison so that there are NO defects in Gene Development › If an error occurs an any phase during development it opens a wide range of genetic disorders

5.  Two Types of Cell Division › Mitosis (Non-reductive Division)  Two Daughter Cells (46 chromosomes each) formed from one parent cell › Meiosis (Reductive Division)  Four Daughter Cells (23 chromosomes each) are formed from one parent cell  Only Seen in Germ Cells (Cells creating Sperm & Egg) › Differences in Mitosis & Meiosis  Different in the 1 st phase of cell division – Crossing over of Genes which can cause disorders but very rare  Prevents the chances of having “clones” as siblings

6.  Division Errors: Nondisjunction › 1 sperm or Egg gets 22 or 24 chromosomes not the required 23 › Error causes defects like…Down Syndrome or Turners Syndrome  Children will suffer from intellectual delays, unusual facial features, congenital malformations  Occurrence: 6-9/1000 live births  95% of individuals with Down Syndrome develop this way

7.  Chromosomal Loss › Turners Syndrome: 45 Chromosomes – Missing a X or Y › 99% miscarriage rate › Features include.. Webbed neck, nonfunctional ovaries, poor development of the cardiac muscle  Unlike Down Syndrome – No real delay in intelligence  Mosaicism › Loss of extra chromosome › Very rare and seen only in 5-10% of Chromosomal abnormalities  Translocation › Transfer of 1 chromosome to a completely different 1 › Results in Down Syndrome because of extra chromosome (Trisomy 21)

8.  Deletion › Part if not all chromosome is lost  1 in 50,000  Causes: Unusual Facial features with round face, wide spread eyes, lower set ears, intellectual disabilities › Williams Syndrome of Micro-deletion  Causes: Intellectual Disabilities, distinctive facial features, heart defects › YCFS  Causes: cleft palate, heart defects, characteristic facial features, learning disabilities

9.  Function of Gene › Produce proteins and to regulate the function and development of the body › Composed of DNA (Double Helix)  A-T and C-G meet up to make gene combinations › Over 3.3 Gene combinations  Genes can turn on and off  Errors occurs when the body does not properly turn gene’s on and off.

10.  Errors caused by… › Transcription › Translation › Mutations  Point Mutations  Insertion and Deletions  Triple Repeat Disorder  Gene Disorders… › Selective Advantage › Single Nucleotide Polymorphisms (SNPs) › Single Gene (Mendelian) Disorders  Autosomal Recessive Disorders  Autosomal Dominant Disorders  X Linked Disorders

11.  TRANSCRIPTION: › Rarely see any errors during this process › DNA unzipping allowing mRNA to make a copy of information › Errors are prevented because of “Proof Reading” enzyme  TRANSLATION: › mRNA travels from nucleus to cytoplasm to create protein

12.  Point Mutations  Most common type caused by single based pair substitution › Missense Mutation : change in triple pair causing the wrong amino acid to attach in a protein chain › Nonsense Mutation: Termination of Protein

13.  Insertion and Deletion: › Most common Insertion: Polio › Most common Deletion: Duchenne Muscular Dystrophy › Frame Shift: Tay-Sachs Disease  Triplet Repeat Expansion: › Over production of codons causing genes to turn off › Causes: Huntington Disease and Fragile X Syndrome

14.  Incidence in genetic diseases depends on the amount of mutations that occur and the amount that are removed  National selection helps eliminate these problem genes › Sickle Cell Anemia

15.  Autosomal Recessive Disorders › Incidents are very rare › 1700 disorders- inherited from mother and father › EXAMPLE: Tay-Sachs which is when the body is unable to properly break down nerve cells causing a build up of toxins in the brain

16.  Autosomal Dominate Disorders › 4500 autosomal disordered identified › 1 in 500 live births › Single abnormal allele › Example: Achondroplasia and Neurofibromatosis

17.  X-Linked Disorders › Mutation in the sex chromosome (X chromosome) › 900 X-Linked Disorders › 25% of males and 10% of females with intellectual/learning disabilities are affected by X-Link Disorder › Example:  Duchenne Muscular Disorder  Mutation in the muscle cell membrane  Fragile X-Syndrome  Most common X-Link Disorder

18.  Genomic Imprinting - Traits are inherited from the mother and father but there is a gene deletion that occurs from either the mother or the father. - Prader-Willi Syndrome which is characterized by short statue, obesity, and intellectual disabilities. - Angelman Syndrome which is characterized by intellectual disabilities and epilepsy. **Reasons for genomic imprinting is remains unclear

19.  Anticipation › Abnormal gene manifest increasing the severity of the disease or disorder with each generation. › Example: Huntington Disease  Caused by a triple repeat in gene formation.  Autosomal dominant progressive neurological disease which is associated with movement and cognitive disorders and impairments which increases with each generation

20.  Mitochondrial inheritance › The genes with-in the DNA can mutate causing the mitochondria to not perform efficiently causing deficient energy production and disease.  EXAMPLE: MELAS which stands for Mitochondrial encephalomymelopathy lactic acid and stroke like episodes.  It is carried on by the female gene only  An unaffected mother is able to pass the deficient gene on to her children both male and female. Males can be effected but they can not be carriers.

21. - The environment can affect the phenotype of an individuals gene’s. - Environmental factors can effect the ways at which gene’s are expressed. - EXAMPLE: 2 nd generation Asians growing up in the U.S. are taller than their parents due to an increase in protein intake during adolescence - Disorders like diabetes, meningomyelocele, cleft palate, pyloric stenosis are affected by both the genotype and phenotype factures.

22.  Humans have 46 complementary genetic chromosomes which determine our physical appearance and biological makeup but effect what we pass on to our offspring.  When genes mutate, split incorrectly, delete or add chromosomes it can have a lasting effect on the outcome of a persons offspring  Many problems can occur during pregnancy however even with all the issues that can occur, 95% of infants are born with out defects.

23.  What is a human cell? Chromosome? Gene?  What errors can occur in Meiosis and Mitosis?  What are the differences between autosomal recessive, autosomal dominant, and X-Linked genetic disorders?  What are the inheritance patterns in single-gene disorders (geno-imprinting, anticipation, and mitochondrial inheritance)?  What environmental factors can also cause issues with development ?

24.  Females have over 2 million Eggs  Trisomy is the common cause of miscarriages  Human genome contains 20,000-25,000 genes. Fruit Fly contains 13,000 and a Round Worm contains 19,000  Chimps share 99% of your human genome  People of all races and geography share 99.9% of the same genetic identity There is only 1% that we do not share. (SNP’s)  Many problems can occur during pregnancy however even with all the issues that can occur, 95% of infants are born with out defects.

25. Batshaw, M. L., Pellegrino, L., Roizen, N.J. (2007). Children with Disabilities (6 th ed., pp 3-20). Baltimore, MD: Paul H Brooks U.S. National Library of Medicine. (2012, July 9). Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Autosomal Recessive. Retrieved July 12, 2012 from http://www.beyondbatten.org/about- prevention.htmlhttp://www.beyondbatten.org/about- prevention.html Mayo Clinic Foundation for Medical Education and Research. (2012, May 24). Autosomal Dominate Inheritance Pattern. Retrieved July 11, 2012 from http://www.mayoclinic. com/health/m edical/IM00991http://www.mayoclinic. com/health/m edical/IM00991 Mayo Clinic Foundation for Medical Education and Research. (2012, May 24). Muscular Dystrophy X-Linked Recessive Inheritance Pattern with Carrier Mother. Retrieved July 11, 2012 from http://www.mayoclinic.com/health/medical/IM02723 http://www.mayoclinic.com/health/medical/IM02723