GENETIC DISORDERS Mistakes in the DNA code MIZZZ

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GENETIC DISORDERS: Mistakes in the DNA code MIZZZ FOSTER © 2015

GENETIC DISORDERS: Mistakes in the DNA code MIZZZ FOSTER © 2015

Quick review of Genes and Proteins • Genes are a sequence of DNA nucleotides

Quick review of Genes and Proteins • Genes are a sequence of DNA nucleotides which code (codons) for the building of a polypeptide chain at the ribosome which will be folded into a protein inside the rough endoplasmic reticulum. • Proteins are long chains of amino acids (polypeptide chains) which are folded into a specific 3 -D shape and have a specific function. They are the foundation of an organism’s physical and behavioral characteristics.

What are genetic mutations? • When a “mistake” is made in the DNA sequence

What are genetic mutations? • When a “mistake” is made in the DNA sequence or chromosome which causes the wrong amino acid or group of wrong amino acids to be placed into a polypeptide chain. • This results a different or altered protein. • Mutation can be GOOD or BAD. • Bad mutations lead to an unhealthy organism which are unfit for their environment. • Good mutations can create a more fit and stable organism and drive evolution.

How do you think the extra set of wings will affect the dragon fly?

How do you think the extra set of wings will affect the dragon fly? • Think of both good and bad effects.

Mutations • Most mutations either occur within the DNA strand or to the chromosomes.

Mutations • Most mutations either occur within the DNA strand or to the chromosomes. • Types of mutations are: Deletion, Insertion, Duplication, Inversion, Substitution • These mutations go unnoticed when they benefit a species, but are noticed when they cause disorders and syndromes.

Review of key terms we should already know. • Autosomes – Any chromosome other

Review of key terms we should already know. • Autosomes – Any chromosome other than a sex chromosomes. 22 pairs of autosomes in a normal human being • Sex Chromosomes- Chromosomes that control the development of sexual characteristics. Humans have two sex chromosomes. • XX = Female XY = Male • Dominant – Allele that is expressed when two alleles are present/Will mask (hide) a recessive • Recessive – Allele that is not expressed unless two copies are present.

Autosomal Dominant Disorders • 1. Huntington’s Disease • 2. Achondroplasia

Autosomal Dominant Disorders • 1. Huntington’s Disease • 2. Achondroplasia

Huntington’s Disease • Huntington's disease (HD) is an inherited, degenerative brain disorder which results

Huntington’s Disease • Huntington's disease (HD) is an inherited, degenerative brain disorder which results in an eventual loss of both mental and physical control. • This disease is caused by duplication of the sequence CAG on chromosome 4. It is dominant • The disease is also known as Huntington's chorea. Chorea means "dance-like movements" and refers to the uncontrolled motions often associated with the disease. • The average life expectancy of the patient once the disease has been diagnosed is about 12 years.

Duplication Mutation: HUNTINGTON DISEASE • Huntington disease is a degenerative disease that affects people

Duplication Mutation: HUNTINGTON DISEASE • Huntington disease is a degenerative disease that affects people as they get older. • The Huntington gene is located on chromosome 4’s short arm and has a sequence of CAG repeats. • Normal people only have 10 – 35 repeats. • People who develop Huntington’s disease have 40 or more repeats. The more repeats the earlier the disease’s symptoms show up in a person. • The earliest documented case was in a 2 year old boy who had 100 repeats of CAG.

Huntington’s • Scientists have discovered that the abnormal protein produced by the Huntington's disease

Huntington’s • Scientists have discovered that the abnormal protein produced by the Huntington's disease gene, which contains an elongated stretch of amino acids called glutamines, binds more tightly to HAP-1 than the normal protein does.

Duplication Mutation: HUNTINGTON DISEASE • All the extra CAG repeats cause the Huntingtin protein

Duplication Mutation: HUNTINGTON DISEASE • All the extra CAG repeats cause the Huntingtin protein to be much larger and have too many glutamines.

Achondroplasia (a. k. a. dwarfism) • Point Mutation, autosomal • Carriers express genes, therefore,

Achondroplasia (a. k. a. dwarfism) • Point Mutation, autosomal • Carriers express genes, therefore, is it dominant or recessive? • Normal life expectancy • There is also a disease called gigantism (Andre the Giant)

Autosomal Recessive Disorders • 1. Cystic Fibrosis • 2. Tay- Sachs • 3. Phenylketonuria

Autosomal Recessive Disorders • 1. Cystic Fibrosis • 2. Tay- Sachs • 3. Phenylketonuria (PKU)

FRAMESHIFT MUTATION • When two or more nucleotides cause two or more amino acids

FRAMESHIFT MUTATION • When two or more nucleotides cause two or more amino acids to be changed resulting in a nonfunctioning or poorly functioning protein. • Can be caused by deletion, insertion, duplication or inversion.

Frameshift Mutation Disease: Autosomal Dominant, Cystic Fibrosis • Cystic Fibrosis- Three nucleotides “G A

Frameshift Mutation Disease: Autosomal Dominant, Cystic Fibrosis • Cystic Fibrosis- Three nucleotides “G A A” have been deleted which results in a frameshift mutation causing two amino acids to be missing from the final cellular membrane protein which absorbs Chlorine. • Cystic fibrosis results in salty skin, greasy stool, phlegm build up in lungs, poor growth. • Found in European Americans and is a recessive gene.

Frameshift Mutation Disease: Cystic Fibrosis • Because cystic fibrosis is a deadly disease many

Frameshift Mutation Disease: Cystic Fibrosis • Because cystic fibrosis is a deadly disease many people who carry the gene go through genetic counseling. • A pedigree is a genetic family tree used in genetic counseling to trace the inheritance of a gene. • Circles are female and squares are men. • Pedigrees allow people to predict the possibility of inheriting a trait.

Tay-Sachs disease • Monogenic, autosomal recessive • Central nervous system degrades, ultimately causing death.

Tay-Sachs disease • Monogenic, autosomal recessive • Central nervous system degrades, ultimately causing death. • Most common among people of Jewish, eastern Europe descent. • Life expectancy is 4 -6 years old.

Tay-Sachs disease • Monogenic, autosomal recessive • Central nervous system degrades, ultimately causing death.

Tay-Sachs disease • Monogenic, autosomal recessive • Central nervous system degrades, ultimately causing death. • Most common among people of Jewish, eastern Europe descent. • Life expectancy is 4 -6 years old.

Point Mutation Disease: Autosomal Recessive PHENYLKETONURIA = PKU • The codon GAT mutated to

Point Mutation Disease: Autosomal Recessive PHENYLKETONURIA = PKU • The codon GAT mutated to GTT in the enzyme responsible for phenylalanine breakdown is nonfunctional. Occurs on chromosome 12. • People with PKU cannot break down phenylalanine instead it builds up as a poison and causes irreversible neurological damage. • Children born normal will develop mental retardation and damaged nerves from consuming foods with phenylalanine.

PKU • Phenylalanine is an essential amino acid and is found in nearly all

PKU • Phenylalanine is an essential amino acid and is found in nearly all foods which contain protein, dairy products, nuts, beans, tofu… etc. • A low protein diet must be followed. • Brain damage can result if the diet is not followed causing mental retardation…and mousy body odor (phenylacetic acid is in sweat). • Life expectancy is normal with proper diet.

Symptoms • • • A musty odor to the skin, hair, and urine. Skin

Symptoms • • • A musty odor to the skin, hair, and urine. Skin problems. Losing weight from vomiting and diarrhea. Acting fussy. Being sensitive to light.

Point Mutation Disease: PHENYLKETONURIA = PKU • They must take care to NOT eat

Point Mutation Disease: PHENYLKETONURIA = PKU • They must take care to NOT eat foods with phenylalanine. • Food labels are required by law to state whether or not phenylalanine is present. • This bull’s eye graphic is a great resource for determining which foods are safe.

Autosomal Codominant Disorder • 1. Sickle Cell Anemia

Autosomal Codominant Disorder • 1. Sickle Cell Anemia

Point Mutation Disease: Autosomal Codominant Sickle Cell Anemia • The codon GAG mutated to

Point Mutation Disease: Autosomal Codominant Sickle Cell Anemia • The codon GAG mutated to GTG which causes the wrong amino acid to be placed in the hemoglobin polypeptide chain. • The point mutation causes hemoglobin to have “sticky” ends and stick together when red blood cells are not carrying oxygen which causes them to elongate into the sickle shape. • When the red blood cells are carrying oxygen they retain a normal round shape. • The constant changing of shape shortens the RBC life to 10 – 20 days instead of 90 – 120 days.

Sickle Cell Anemia • Caused by a point mutation • An inherited, chronic disease

Sickle Cell Anemia • Caused by a point mutation • An inherited, chronic disease in which the red blood cells, normally discshaped, become crescent shaped. As a result, they function abnormally and cause small blood clots. These clots give rise to recurrent painful episodes called "sickle cell pain crises".

Point Mutation Disease: Sickle Cell Anemia • Found primarily in African descendants and African

Point Mutation Disease: Sickle Cell Anemia • Found primarily in African descendants and African Americans. • In Africa sickle cell anemia protects against malaria because the malaria parasite is unable to stay inside the changing red blood cells. • In Africa sickle cell anemia increases children’s rate of survival who carry the gene which results in a high portion of the population being heterozygous for sickle cell anemia.

Sex-Linked Genetic Disorder • Mutations found on the sex chromosomes or affecting the sex

Sex-Linked Genetic Disorder • Mutations found on the sex chromosomes or affecting the sex chromosomes as we saw in Kleinfelter’s and Turner’s syndromes. • Most sex-linked genetic disorders are found on the X chromosome and passed from mother to son. • Women can sometimes have the disorder if they have a carrier mother and an affected father.

Sex- Linked Genetic Disorders X-Linked Recessive • 1. Hemophilia • 2. Duchenne Muscular Dystrophy

Sex- Linked Genetic Disorders X-Linked Recessive • 1. Hemophilia • 2. Duchenne Muscular Dystrophy • 3. Colorblindness

Hemophilia, the royal disease • Hemophilia is the oldest known hereditary bleeding disorder. •

Hemophilia, the royal disease • Hemophilia is the oldest known hereditary bleeding disorder. • Caused by a recessive gene on the X chromosome. • There about 20, 000 hemophilia patients in the United States. • One can bleed to death with small cuts. • The severity of hemophilia is related to the amount of the clotting factor in the blood. About 70% of hemophilia patients have less than one percent of the normal amount and, thus, have severe hemophilia.

Sex-linked genetic disorder: HEMOPHILIA • Sex-linked genetic disorder on the X chromosome which affects

Sex-linked genetic disorder: HEMOPHILIA • Sex-linked genetic disorder on the X chromosome which affects blood clotting factors. • It is mostly found in males but can show up in females. • People with hemophilia are at a high risk of bleeding to death. • Hemophilia caused the death of many males in Queen Victoria’s family line. • Women can have hemophilia if it is on both X chromosomes.

Muscular Dystrophy • What Is Muscular Dystrophy? Muscular dystrophy is a disease in which

Muscular Dystrophy • What Is Muscular Dystrophy? Muscular dystrophy is a disease in which the muscles of the body get weaker and slowly stop working because of a lack of a certain protein • Caused by mutation on the X chromosome. • Life expectancy is 18 to early 20’s.

Muscular Dystrophy • • • Frequent falls Difficulty getting up from a lying or

Muscular Dystrophy • • • Frequent falls Difficulty getting up from a lying or sitting position Trouble running and jumping Large calf muscles Learning disabilities

Sex-linked genetic disorder: COLORBLINDNESS • Sex-linked gene found on the X which interferes with

Sex-linked genetic disorder: COLORBLINDNESS • Sex-linked gene found on the X which interferes with a person’s ability to see color. • Some people have blindness in pairs of colors and few can see no color. • Mostly found in males and inherited from their mothers. • Women can be colorblind if they carry the gene on both x chromosomes.

Color Blindness • Cause: x-linked recessive • 1/10 males have, 1/100 females have. Why

Color Blindness • Cause: x-linked recessive • 1/10 males have, 1/100 females have. Why the difference? • Individuals are unable to distinguish shades of red-green. • Are you color blind? • Normal life expectancy

Sex-linked genetic disorder: COLORBLINDNESS • Colorblind test

Sex-linked genetic disorder: COLORBLINDNESS • Colorblind test

Sex-linked genetic disorder: Y-chromosome diseases Lack of sperm production • This mutation happens on

Sex-linked genetic disorder: Y-chromosome diseases Lack of sperm production • This mutation happens on the chromosome in an individual. They may not have children as a result. Retinitis Pigmentosa • A chronic hereditary eye disease characterized by black pigmentation and gradual degeneration of the retina.

The very tragic disease… hairy ears Caused by mutation on Y chromosome, which are

The very tragic disease… hairy ears Caused by mutation on Y chromosome, which are rare • symptoms…hairy ears • Only 1 cure known….

SHAVE THEM !!!!!!!

SHAVE THEM !!!!!!!

CHROMOSOMAL MUTATIONS • Mutations which affect the entire chromosome by extra copies, deletions, parts

CHROMOSOMAL MUTATIONS • Mutations which affect the entire chromosome by extra copies, deletions, parts missing or translocated. Whole groups of proteins are affected. • Karyotypes are a photograph of a person’s chromosomes. Karyotypes are used to diagnose chromosomal mutations. • Normal karyotypes should only have two chromosomes at each number. • A person receives a set of chromosomes 1 -23. One from mom and one from dad.

Nondisjunction Two copies of a chromosome do not properly segregate during meiosis and end

Nondisjunction Two copies of a chromosome do not properly segregate during meiosis and end up in the same gamete leaving another gamete without the chromosome. Nondisjunction causes polysomy and monosomy.

Chromosomal Mutation: POLYSOMY – more than the correct number of chromosomes • More than

Chromosomal Mutation: POLYSOMY – more than the correct number of chromosomes • More than 2 copies of a single chromosome resulting in excess proteins being synthesized.

Downs Syndrome: Trisomy 21 • Three copies of chromosome 21. A person affected has

Downs Syndrome: Trisomy 21 • Three copies of chromosome 21. A person affected has mental retardation, developmental delays, shorter stature, and some organ dysfunction. Modern medicine has helped to increase life span. • Downs Syndrome can be the result of gametes having an extra chromosome 21 or the early embryonic cells had a case of nondisjunction.

Down’s Syndrome or Trisomy 21

Down’s Syndrome or Trisomy 21

Symptoms of Down Syndrome • • • Upward slant to eyes. Small ears that

Symptoms of Down Syndrome • • • Upward slant to eyes. Small ears that fold over at the top. Small, flattened nose. Small mouth, making tongue appear large. Short neck. Small hands with short fingers.

Symptoms of Down Syndrome • • • Low muscle tone. Single deep crease across

Symptoms of Down Syndrome • • • Low muscle tone. Single deep crease across center of palm. Looseness of joints. Small skin folds at the inner corners of the eyes. Excessive space between first and second toe. In addition, down syndrome always involves some degree of mental retardation, from mild to severe. In most cases, the mental retardation is mild to moderate.

XXY • Males with some development of breast tissue normally seen in females. •

XXY • Males with some development of breast tissue normally seen in females. • Little body hair is present, and such person are typically tall, have small testes. • Infertility results from absent sperm. • Evidence of mental retardation may or may not be present. • Life expectancy is average.

Kleinfelter’s syndrome (or Klinefleter’s) • Disorder occurring due to nondisjunction of the X chromosome.

Kleinfelter’s syndrome (or Klinefleter’s) • Disorder occurring due to nondisjunction of the X chromosome. • The Sperm containing both X and Y combines with an egg containing the X, results in a male child. • The egg may contribute the extra X chromosome.

Klinefelter’s Syndrome • The XXY male is sterile and can not father children. •

Klinefelter’s Syndrome • The XXY male is sterile and can not father children. • They exhibit language impairment, breast cancer, arthritis, varicose veins, pulmonary disease, and osteoporosis. • They have male and female characteristics, but do have male genitalia.

Chromosomal Mutation: MONOSOMY Less than the correct number of chromosomes are present • Monosomy

Chromosomal Mutation: MONOSOMY Less than the correct number of chromosomes are present • Monosomy is when only one copy of a specific chromosome is present in an organism resulting in a lack of protein.

Turner’s Syndrome • Monosomy of the sex chromosomes. • Only found in females, results

Turner’s Syndrome • Monosomy of the sex chromosomes. • Only found in females, results with only one X chromosomes. • Women with Turner’s syndrome are sterile, short stature, no ovarian development, no puberty, webbed neck, thyroid and skeletal problems. No menstruation.

Turner’s Syndrome

Turner’s Syndrome