Post on 23-Dec-2015
transcript
Genetic &
Developmental Disorders
By: Jenna M. Filipone
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
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
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
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
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
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)
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
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.
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
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
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
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
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
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
Single Gene (Mendelian) Disorders
Autosomal Dominate Disorders › 4500 autosomal
disordered identified › 1 in 500 live births › Single abnormal allele› Example:
Achondroplasia and Neurofibromatosis
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
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-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
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
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.
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.
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.
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 ?
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.
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