Gene Mutations PDF

# Gene Mutations - **Sickle shaped red blood cells** - An image of red blood cells with a few being sickle shaped is shown. - **What is a gene mutation?** - Mutations are changes in genetic material - changes in DNA code - thus a change in a gene(s) - In gene mutations, the DNA code will have...

# Gene Mutations - **Sickle shaped red blood cells** - An image of red blood cells with a few being sickle shaped is shown. - **What is a gene mutation?** - Mutations are changes in genetic material - changes in DNA code - thus a change in a gene(s) - In gene mutations, the DNA code will have a base (or more) missing, added, or exchanged in a codon. - **How common are mutations?** - Mutations occur at a frequency of about 1 in every 1 billion base pairs. - Everybody has about 6 mutations in each cell in their body! - **Mutagens** - What causes mutations? Natural errors or an environmental event - What is a mutagen? Something that causes the DNA code to change (mutate) - x-ray, chemicals, UV light, radiation, etc. - What happens to a person who has a mutation? - **If I have that many mutations, why don't I look weird?** - Mutations are not always seen. The affected gene may still function. - Mutations may be harmful. - Mutations may be beneficial. - Mutations may have no effect on the organism. - **How do mutations affect a population?** - Mutations are a major source of genetic variation in a population increasing biodiversity. - Some variations may help them to survive better. - An image showing a large number of people with a few people being different from the others is shown. - **How are mutations inherited?** - Only mutations in gametes (egg & sperm) are passed onto offspring. - Mutations in body cells only affect the organism in which they occur and are not passed onto offspring. - **Types of Gene Mutations** - Point mutation occurs when the base sequence of a codon is changed. (ex. GCA is changed to GAA). - There are 3 types - Substitution - Deletion - Insertion Also called frameshift mutations - **Substitution Mutations** - Normal DNA: CGA - TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA - TGC - TTC - Alanine - Threonine - Lysine - What has happened to the DNA? - This is a substitution mutation. - A single nitrogen base is substituted for another in a codon. - It may or may not affect the amino acid or protein. - Normal DNA: CGA – TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA-TGC-TTC - Alanine - Threonine - Lysine - **TRY THIS!** - On your notebook paper write: The cat ate the rat. - Change one letter in the sentence to represent a substitution mutation. - Think-Pair-Share. - **Analogy** - 3 letter words because codons are 3 letters - The cat ate the rat. - SUBSTITUTION - The cat ate the rat. - May have little effect. You still have the idea like a typo on a test. - The hat ate the rat. - Changes the thought of the sentence. The effect depends on where the substitution happens. - **Insertion Mutations** - Normal DNA: CGA - TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA - TAG - CAT - C - Alanine - Isoleucine - Valine - What has happened to the DNA? - This is an insertion mutation. - A nitrogen base is inserted/added to the sequence. - It causes the triplet "frames" to shift. - It always affects the amino acids and consequently, the protein. - Normal DNA: CGA - TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA - TAG - CAT - C - Alanine - Leucine - Valine - **TRY THIS!** - On your notebook paper write: The cat ate the rat. - Insert a letter into any word above. - Rewrite the sentence. Each word must have only 3 letters to represent the codon. - Discuss the effects on the insertion. - Think-Pair-Share. - **Analogy** - Insertion - The cat ate the rat. - The cca tat eth era t. - Inserting the c causes a FRAMESHIFT - THE SENTENCE NO LONGER MAKES SENSE!! Insertions may have huge effects. - **Deletion Mutations** - Normal DNA: CGA - TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA - TCA - TC - Alanine - Serine - What has happened to the DNA? - This is a deletion mutation. - A nitrogen base is deleted/removed from the sequence. - It causes the triplet "frames" to shift. - It always affects the amino acids and consequently the protein. - Normal DNA: CGA-TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA-TCA-TC - Alanine - Serine - **TRY THIS!** - Write the sentence on your paper: The cat ate the rat. - Delete one letter from any word. - Rewrite the sentence. Remember: each word can only have 3 letters. - Think-Pair-Share. - **Analogy** - DELETION - The cat ate the rat. - The ata tet her at - FRAMESHIFT - The sentence no longer makes sense!! Deletions can have huge effects. - **Gene Mutations** - Which mutation would have the least affect on an organism? - Normal DNA: CGA - TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA - TGC - ATT - Alanine - Threonine - stop - Mutated DNA: CGA - TGC - ATG - Alanine - Threonine - Tyrosine - Substitution has the least affect because it changes only one amino acid or it may change no amino acid. - **Gene Mutations** - An example of a substitution mutation is sickle cell anemia. - Only one amino acid changes in the hemoglobin. - The hemoglobin still functions but it folds differently changing the shape of the rbc. - An image of red blood cells with a few being sickle shaped is shown. - Another image of normal red blood cells is shown. - **Gene Mutations** - Which mutation would have the most affect on an organism? - Insertion and deletion mutations have the most effect on an organism because they affect many amino acids and consequently the whole protein. - Normal DNA: CGA-TGC - ATC - Alanine - Threonine - stop - Mutated DNA: CGA-TCA-TC - Alanine - Serine - Mutated DNA: CGA-TAG-CAT-C - Alanine - Leucine - Valine - **Gene Mutations** - Huntington's Disease is caused by an insertion mutation. - People with this disorder have involuntary movement and loss of motor control. They eventually have memory loss and dementia. The disease is terminal. - An image shows a chromosome with a section labeled Huntington's disease. This is located at the end of chromosome 4. - The text "Huntington Disease Located on chromosome 4 First Gene Disease Mapped" is also shown. - **Gene Mutations** - When does a gene mutation have the greatest affect on an organism? - When it occurs in the gamete (egg or sperm) or early in embryonic development (in stem cells or first few days). - An image shows an egg being fertilized. Another image shows a four-cell zygote. Another image shows an embryo. - **1) Trisomy 21 (Down syndrome)** - A karyotype of a male with Down syndrome is shown. - An image of a child with Down syndrome is shown. - **Ophthalmology clinical features** - Myopia - Cataract - Glaucoma - Brushfield spots (speckled irises) - Nystagmus - Strabismus - Screen at birth, 6 mo. Than annually - **Musculoskeletal clinical features** - Short neck, redundant skin - Short metacarpals and phalanges - Short 5th digit with Clinodactyly - Single transverse palmer creases - Wide gap between 1 & 2nd toes - Short sternum - Atlantoaxial instability (screen each visit) - Hip dysplasia - Recurrent joints dislocation - **Cardiac clinical finding** - Endocardial cushing defect (AVSD) MOST COMMON - Ventricular septal defect - Atrial septal defect - Patent ductus arteriosus - Pulmonary hypertension - Screen at birth - **Facial clinical features** - Brachycephaly - Up slanted palpebral fissures - Epicanthal folds - Three fontanels - Flat nasal bridge, small nose - Short hard palate - Microcephaly - Low set ears - Hearing loss - Screen at birth - Hearing screen - Recurrent otitis media than annually - **Hematological finding** - Transient myeloproliferative dis. - ALL (>1y.o) - AML (<10) - Screen at birth - **Endocrine finding** - Hypothyroidism - Hyperthyroidism - Diabetes mellitus - Infertility Screen at birth, 6 mo. than annually - Obesity - **Neuropsychiatric finding** - Hypotonia - Developmental delay - Autism - Seizure - Screen each visit - **Gastrointestinal finding** - Duodenal atresia - Annular pancreas - Tracheoesophageal fistula - Hirschsprung disease - Imperforated anus - Neonatal cholestasis - Celiac disease (Screen at 2y.o) - **Causes** - Nondisjunction (95%) - Translocation (4%) - Mosaic (1%) - **Recurrence** - 1% - **When the recurrence become 100%?** - If a parent has 21:21 translocation - **Prenatal screen lab finding?** - Low a feto protein - Low estriol - High hCG and high inhibin - **Maternal Age (yrs)** - 30 - 35 - 40 - 45 - 50 - 55 - **1 in DOWN SYNDROME** - 950 - 1:350 - 1:100 - 1:30 - 1:188 - 1:112 - **Respiratory finding:** - Obstructive sleep apnea Screen at 1.0 - Recurrent infections - **2) Trisomy 18 (Edwards syndrome)** - A karyotype of a female with Edwards syndrome is shown. - 3 images of children with Edward's syndrome are shown. - **Clinical features** - Rocker bottom feet - Overlapping fingers - Clenched fist - Short sternum - Hypoplastic nails - Hypoplastic nasal alae - IUGR - Intellectual disability - Microcephaly - Hypertonia - Prominent occiput - Micrognathia - Limited hip abduction - Cleft lip / palate - **2nd most common autosomal trisomy** - **Most common cardiac defect?** - Ventricular septal defect (VSD) - Atrial septal defect (ASD) - PDA - **Most common cause of death?** - Central apnea - **Prenatal screen lab finding?** - Low a feto protein - Low estriol - Low hCG - **Prognosis** - 50% die in the 1st week of life - 90% die by 1 year of age - **3) Trisomy 13 (Patau syndrome)** - A karyotype of a female with Patau syndrome is shown. - 3 images of children with Patau syndrome are shown. - **Clinical features** - Midline defect - Aplasia cutis congenita - Microphthalmia - Microcephaly - Postaxial polydactyly - Hypotonia - Holoprosencephaly - Hypoplastic/absent ribs  - Abdominal wall defect - Deafness - Colobomas - Capillary hemangioma - Genital anomalies - Clenched fist - **3rd most common autosomal trisomy** - **Most common cardiac defect ?** - Ventricular septal defect (VSD) - Atrial septal defect (ASD) - PDA - **Most common cause of death?** - Central apnea - **Prognosis** - 70% die in the 1st 3 months of life - 95% die by 3 years of age - Rarely reach up to 10 years - **4) Turner Syndrome** - A karyotype of a female with Turner syndrome is shown. - 3 images of children with Turner syndrome are shown. - **Clinical features** - Short stature - Lymphedema of hands & feet - Shield chest - Cubitus valgus - Low posterior hairline - Posterior rotated ears - Webbed neck - Short 4th metacarpal bone - Normal intelligence (except Math) - **What is the most consistent finding?** - Short stature (SHOX gene) - Ovarian dysgenesis - **What is the most common cardiac defect?** - Bicuspid aortic valve - Coarctation of aorta - **Labs finding?** - High FSH - High FSH/LH - Low estradiol - **What is the most common renal anomaly?** - Horseshoe kidney - Double collecting system - **Increases risk of:** - Hypothyroidism - Hashimoto disease - Celiac disease - Inflammatory bowel disease - **Increases risk of which Malignancy?** - Gonadoblastoma - **Treatment** - Growth hormone - Estrogen therapy