Genetic & Developmental Disorders

1. Genetic & Developmental Disorders By: Jenna M. Filipone

2. Lesson Objectives... • 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. What is a Genetic Disorder? • 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. Genetic Disorders…The Cell • 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. Cell Division • 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 1st phase of cell division – Crossing over of Genes which can cause disorders but very rare • Prevents the chances of having “clones” as siblings

6. Cell Errors: Chromosomes • 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. Types of Errors in Chromosomes • 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. Types of Errors in Chromosomes Cont. • 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. Gene’s and their Functions • 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. Gene Errors and Disorders • 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 & Translation • 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. Gene Mutations • 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. Gene Mutations Cont. • 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. Selective Advantage • 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. Single Gene (Mendelian) Disorders • 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. Single Gene (Mendelian) Disorders • Autosomal Dominate Disorders • 4500 autosomal disordered identified • 1 in 500 live births • Single abnormal allele • Example: Achondroplasia and Neurofibromatosis

17. Single Gene (Mendelian) Disorders • 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. Revising Mendelian Genetics • 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-WilliSyndrome 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. Revising Mendelian Genetics • 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. Revising Mendelian Genetics • 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. Environmental Influences • The environment can affect the phenotype of an individuals gene’s. • Environmental factors can effect the ways at which gene’s are expressed. • EXAMPLE: 2nd 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. Summary • 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. REVIEW • 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. FYI… Interesting Info • 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. References Batshaw, M. L., Pellegrino, L., Roizen, N.J. (2007). Children with Disabilities(6th 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.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/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