Extending Mendelian Genetics

Disorders caused by recessive alleles Two copies of the recessive allele must be present for a person to have the disorder Often appear in offspring of parents who are both heterozygous (carriers)

Sickle Cell Anemia Recessive genetic disorder Mutated allele that produces a defective form of the protein hemoglobin Hemoglobin Found in red blood cells (RBCs) Binds oxygen and transports it throughout the body

Sickle Cell Anemia Sickle cell anemia causes a defective form of hemoglobin that causes many RBCs to bend into a sickle shape Less oxygen can be carried in the blood Cells tend to get stuck in blood vessels, cutting off blood supply to organs

Malaria Benefits of sickle cell anemia? Protects the cells of heterozygous individuals from the effects of malaria A disease caused by a parasitic protozoan that invades RBCs Sickled cells kill the parasite The individual’s normal RBCs can deliver oxygen In this case, heterozygous individuals have a better survival rate in areas plagued by malaria

Cystic Fibrosis (CF) Most common fatal, hereditary, recessive disorder amongst Caucasians 1/25 Caucasian individuals has at least one copy of a defective gene that makes a protein necessary to move chloride into and out of cells 1/2,500 Caucasian infants in the USA is homozygous for the cf allele

Cystic Fibrosis (CF) The airways of the lungs become clogged with thick mucus, and the ducts of the liver and pancreas become blocked There is no known cure

Disorders caused by dominant alleles are far less common than recessive disorders

Huntington’s Disease (HD) Genetic disorder caused by a dominant allele Causes a repeat of a gene sequence, causing cell death in the brain area First symptoms: mild forgetfulness and irritability Appears in victims in the 30’s and 40’s

Huntington’s Disease (HD) Secondary symptoms: loss of muscle control, uncontrollable physical spasms, severe mental illness…eventually death Most people do not know they have the disease until after they have had children Unknowingly the gene is passed on

Males and females can differ in sex-linked traits Sex-linked genes: genes located on the sex chromosomes

Autosomal Autosomal gene: will appear in both sexes equally Found on chromosomes other than the X or Y

Sex-linked Usually males are the only sex affected Why? Males only have one X A female carrying a recessive allele on one chromosome will not exhibit the condition if there is a dominant allele on the other one

Treating Genetic Disorders Most genetic disorders cannot be cured Gene Therapy Replacing defective recessive genes with copies of healthy ones Outlook is promising

Expression of sex-linked genes X chromosome inactivation: process that occurs in female mammals in which one of the X chromosomes is randomly turned off in each cell

Incomplete Dominance In some organisms an individual displays a phenotype that is intermediate between the two parents Examples Snapdragon flowers: red and white flowers produce pink flowers Caucasian child: parent with curly hair and parent with straight hair has wavy hair

Incomplete dominance

Codominance Two dominant alleles are expressed at the same time Different than incomplete dominance because both traits are displayed Example: blood type

Multiple Alleles Genes with three or more alleles i.e. blood type in humans ABO blood types are determined by 3 alleles IA, IB, and i

Multiple Alleles A and B are carbohydrates on the surface of red blood cells i allele has no carbohydrates on the surface IA, IB, are dominant to i but neither IA, IB dominant over each other (they are codominant) Possible blood types: A (IA IA or IAi) B (IB IB or IBi) AB (IA IB) O (ii)

Polygenic trait When several genes influence a character The genes may be on the same chromosome or on different chromosomes Determining the effect of any one of these genes is difficult

Polygenic traits Due to independent assortment and crossing-over during meiosis, many different combinations appear in offspring Polygenic characters in humans: eye color, height, weight, hair and skin color

epistasis Process by which a epistatic gene can interfere with the expression of other genes Albinism: a single epistatic gene interferes with the expression of other genes

The environment interacts with genotype Phenotype often depends on conditions in the environment The plant hydrangea has flowers that can be blue to pink, depending on the pH of the soil Acidic soil: blue flowers Neutral to basic: pink flowers Temperature can determine sex of sea turtles and other species In humans Height is affected by nutrition Skin color is affected by exposure to the sun

Gene linkage and mapping Gene linkage was explained through fruit flies Linked genes are on the same chromosome The closer two genes are, the more likely it is that they will be inherited together The closer two genes are, the more likely they are to stay together when cross-overs in meiosis take place

Linkage maps estimate distances between genes Maps of relative locations of genes on a chromosome

Human genetics & pedigrees Human genetics follows the patterns seen in other organisms Females can carry sex-linked genetic disorders

Hemophilia Recessive genetic disorder Impairs the blood’s ability to clot Sex-linked trait More than a dozen genes code for the proteins involved in blood clotting A mutation of one of these genes on the X chromosome causes hemophilia A

A pedigree is a chart for tracing genes in a family Shows how a trait is inherited over several generations Particularly helpful in finding out if a person is a carrier for a genetic disease

Several methods help map human chromosomes Karyotype: An array of the chromosomes found in an individual’s cells at metaphase of mitosis Arranged in homologous pairs and in order of diminishing size

Trisomy 3 copies of chromosomes instead of 2 3 copies of chromosome #21 instead of 2? Down syndrome, or trisomy 21

What causes trisomy? Older mothers are more likely to have children with Down syndrome Mothers under 30 years old: 1/1500 births Mothers over 37 years old: 1/290 births Mothers over 45 years old: 1/46 births

Trisomy Eggs are present in the ovaries since birth and over time can accumulate damage (What about males? They produce new sperm throughout their adult lives) Older pregnant women may be advised to undergo prenatal testing that includes fetal karyotyping

Disjunction When sperm and eggs cells form, each chromosome and its homologue separate

What causes trisomy? Nondisjunction: If one or more chromosomes fail to separate properly One new gamete ends up receiving both chromosomes and the other gamete receives none A normal gamete and one with 2 copies fuse during fertilization, causing trisomy

Mutations Changes in an organism’s chromosome structure 4 Main Types Deletion Duplication Inversion Translocation