Human Genetics. Ch 14: Autosomal Dominant, Autosomal Recessive, and Sex-linked Disorders and Pedigrees. Biology

Transcription

1 Human Genetics Ch 14: Autosomal Dominant, Autosomal Recessive, and Sex-linked Disorders and Pedigrees Biology

2 What is the difference between an Autosome and a Sex-chromosome? Autosomes are the first 22 homologous pairs of human chromosomes that do not influence the sex of an individual. Sex Chromosomes are the 23 rd pair of chromosomes that determine the sex of an individual.

3 Autosomal Traits Genes located on Autosomes control Autosomal traits and disorders. 2 Types of Traits: Autosomal Dominant Autosomal Recessive

4 Autosomal Dominant Traits What do you remember about normal Dominant and recessive rules from last chapter? Hint: What does the heterozygote express?

5 Autosomal Recessive Traits Aa called a Carrier because they carry the recessive allele and can pass it on to offspring, but they do not express the trait. What alleles have to be present for a recessive trait to show? How many of them?

6 Sex-Linked Traits Sex-linked traits are produced by genes only on the X chromosome. They are always attached to the X chromosome X A X a They can be Dominant or Recessive. A = dominant a = recessive Most Sex-linked traits are Recessive!

7 Sex-Linked Dominant Traits In these cases, the disease or trait is dominant. If you get one copy of the X chromosome with this allele you display this disease or trait. Affects Males and Females with equal chance. Usually these disease are lethal in men. Not as lethal in woman Women may have one normal copy of the gene. This delays the effects or onset of the disease. Possible Genotypes: Sex-linked Dominant trait Expresses Trait: Male - X A Y Female - X A X A or X A X a No Expression: Male - X a Y Female - X a X a

8 Sex-Linked Recessive Traits In these cases, the disease is recessive. These occur more in males then females Males only get 1 X chromosome. If the X chromosome carries this recessive trait it is displayed. Females get 2 X Chromosomes Much less likely to display this trait: need 2 copies. Females can carry the disease and pass it on to their sons. Genotypes: Sex-linked Recessive trait Expresses Trait: Male - X a Y Female - X a X a No Expression: Male - X A Y Female - X A X A or X A X a (Carrier)

9 Albinism 1 in 17,000 births no pigmentation in hair, skin, eyes eye sensitivity and vision problems UV radiation (sun) can easily damage skin 1. Craig and Nina are married and have four children. Both Craig and Nina have brown eyes and hair and light-medium skin. However, 2 of their 4 children have albinism. (Use the letters AA, Aa, or aa.) What is Craig's genotype? What is Nina's genotype? What is the probability that their next child will also have albinism?

10 Cystic Fibrosis Cystic Fibrosis 1 in approximately 2000 births defective CFTR gene...protein pump in cell membrane not made properly or at all mucus clogs lung, liver, and pancreas affects young children to young adults high mortality rate life expectancy currently into the 30s (if given the best care/treatment) NO cure yet A couple in whom the woman is a carrier and the man has cyctic fibrosis of the gene for cystic fibrosis have two children who have cystic fibrosis. (Use the letters FF, Ff, or ff.) What would be the genotypes of the parents? What would be the genotype for their children with CF? What is the probability that their next child will have cystic fibrosis?

11 Achondroplasia The most common form of dwarfism Aa genotype = achondroplasia Matt and Amy Roloff have four children. Although Matt and Amy are both little people, they do not have the same type of dwarfism. Amy has achondroplasia, which is a dominant allele disorder. Their children are: twins Zach and Jeremy, Molly, and Jake. Three of the four children are average height. Zach has achondroplasia like his mother. Show the results of the Roloff family in a Punnett square. Matt (aa) is normal or does NOT have achondroplasia. Amy has achondroplasia (Aa).

12 How to Construct a Pedigree: A Pedigree is a visual showing the pattern of inheritance for a trait. (Family tree) A pedigree is a chart of the genetic history of family over several generations. Scientists or a genetic counselor would find out about your family history and make this chart to analyze.

13 How to Construct a Pedigree: Symbols and Rules: Male = Female = Affected = Unaffected = Carrier = Link parents together with a line and then make a vertical line to connect to offspring.

14 How to Construct a Pedigree: Fraternal twins Married Couple Siblings Identical twins

15 Rule Practice: Label the rest of the individuals on the pedigree below. Mother

16 Autosomal Dominant Traits Heterozygotes are affected Affected children usually have affected parents. Two affected parents can produce an unaffected child. (Aa x Aa) Two unaffected parents will not produce affected children. (aa x aa) Both males and females are affected with equal frequency. Pedigrees show no Carriers.

17 Examples of Autosomal Dominant Disorders Dwarfism Polydactyly and Syndactyly Hypertension Hereditary Edema Chronic Simple Glaucoma Drainage system for fluid in the eye does not work and pressure builds up, leading to damage of the optic nerve which can result in blindness. Huntington s Disease Nervous system degeneration resulting in certain and early death. Onset in middle age. Neurofibromatosis Benign tumors in skin or deeper Familial Hypercholesterolemia High blood cholesterol and propensity for heart disease Progeria Drastic premature aging, rare, die by age 13. Symptoms include limited growth, alopecia, small face and jaw, wrinkled skin, atherosclerosis, and cardiovascular problems but mental development not affected.

18 Autosomal Dominant Pedigree Draw a Pedigree showing a cross between Heterozygous parents that have 2 boys and 2 girls. (Show all possibilities) Genotypes of Affected and Unaffected: AA and Aa = Affected aa = Unaffected Aa Aa aa Aa Aa AA

19 Autosomal Recessive Traits Heterozygotes are Carriers with a normal phenotype. Most affected children have normal parents. (Aa x Aa) Two affected parents will always produce an affected child. (aa x aa) Both parents have to be Carriers to produce an affected offspring.

20 Autosomal Recessive Traits Close relatives who reproduce are more likely to have affected children. Both males and females are affected with equal frequency. Pedigrees show both male and female carriers.

21 Examples of Autosomal Recessive Disorders Congenital Deafness Diabetes Mellitus Sickle Cell anemia Albinism Phenylketoneuria (PKU) Inability to break down the amino acid phenylalanine. Requires elimination of this amino acid from the diet or results in serious mental retardation. Galactosemia enlarged liver, kidney failure, brain and eye damage because can t digest milk sugar Cystic Fibrosis affects mucus and sweat glands, thick mucus in lungs and digestive tract that interferes with gas exchange, lethal. Tay Sachs Disease Nervous system destruction due to lack of enzyme needed to break down lipids necessary for normal brain function. Early onset and common in Ashkenazi Jews; results in blindness, seizures, paralysis, and early death.

22 Autosomal Recessive Pedigree Draw a Pedigree showing a cross between Heterozygous parents that have 2 boys and 2 girls. (Show all possibilities) Genotypes of Affected and Unaffected: AA=Unaffected Aa=Carrier, Unaffected aa=affected Aa Aa aa Aa Aa AA

23 Sex-Linked Recessive Traits More males than females are affected. An affected son can have 2 normal parents. (X A Y x X A X a ) For a daughter to have the trait, her father must express the trait AND her mother must have it or be a carrier. (X a Y, X a X a, X A X a )

24 Sex-Linked Recessive Traits The trait often skips a generation from the grandfather to the grandson. If a woman has the trait (X a X a ), all of her sons will be affected. Pedigrees show only female carriers. No male carriers exist Either have the trait or not.

25 Examples of Sex-Linked Recessive Disorders Red/Green Colorblindness Difficulty perceiving differences between colors (red or green, blue or yellow). Hemophilia Absence of one or more proteins necessary for normal blood clotting. Deafness Cataracts opacity in the lens that can lead to blindness Night blindness (Nyctalopia) rods do not work so that can not see in the dark Glaucoma pressure in the eye that can lead to optic nerve damage and blindness Duchenne Muscular Dystrophy progressive weakness and degeneration of skeletal muscles that control movement due to absence of dystrophin (protein that maintains muscle integrity). Mainly in boys, onset 3-5 yrs, by 12 years can t walk, and later needs respirator.

26 Sex-Linked Recessive Pedigree Draw a Pedigree showing a cross between a Red eyed Male fruit fly and a Carrier Female fruit fly which have 2 males and 2 females. (Show all possibilities) Red is dominant to white. Genotypes of Parents: Male = X R Y Female = X R X r X R Y X R X r X R Y X r Y X R X R X R X r

27 Characteristics of Autosomal Dominant, Autosomal Recessive, and Sex-linked Recessive Traits In groups, analyze your notes on each type of disorder and examine the pedigrees. Come up with rules/characteristics for each type of Trait.

28 Karyotype A karyotype is simply a picture of a person's chromosomes. Chromosomes are arranged in order from largest to smallest. Sex chromosomes are always shown last

29 Karyotype Karyotyping is a test to examine chromosomes in a sample of cells. This can help identify genetic problems as the cause of a disorder or disease. This test can: Count the number of chromosomes Look for structural changes in chromosomes Look for mutations

30 What are Chromosomal Mutations? Damage to chromosomes due to physical or chemical disturbances or errors during meiosis. Two Types of Chromosome Mutations: 1. Chromosome Structure 2. Chromosome Number

31 Problems with Chromosome Number 1. Monosomy only one of a particular type of chromosome (2n -1) 2. Trisomy having three of a particular type of chromosome (2n + 1)

32 Problems with Chromosome Number 3. Polyploidy having more than two sets of chromosomes; triploids (3n = 3 of each type of chromosome), tetraploids (4n = 4 of each type of chromosome).

33 Problems with Chromosome Structure: 1. Deletion during cell division, especially meiosis, a piece of the chromosome breaks off, may be an end piece or a middle piece (when two breaks in a chromosome occur). 2. Inversion a segment of the chromosome is turned 180, same gene but opposite position

34 Problems with Chromosome Structure: 3. Translocation movement of a chromosome segment from one chromosome to a non-homologous chromosome 4. Duplication a doubling of a chromosome segment because of attaching a broken piece form a homologous chromosome, or by unequal crossing over.

35 How do you think Chromosomal Mutations with differing number of chromosomes develops? Monosomy and Trisomy due to Nondisjunction members of homologous chromosomes do not move apart in Meiosis I or sister chromatids do not separate during Meiosis II This leaves one cell with too few chromosomes and one cell with too many.

36 How do you think Chromosomal Mutations with differing number of chromosomes develops? Polyploidy is common in the plant kingdom, spontaneous origin of polyploid individuals plays important role in evolution of plants. In the animal kingdom, natural occurrence of polyploids is extremely rare. In general, polyploids are more nearly normal in appearance than having monosomy or trisomy, which is more disruptive to have one extra chromosome in a pair.