Inheritance Patterns & Human Genetics Sex chromosomes form pairs and segregate during meiosis I just like the 22 autosomes In mammals and most insects, males are XY and females are XX (Also XX/X0 system, ZW system, haploploidy and non-genetic systems) Leads to 50/50 chance male or females

Sex Linkage Presence of a gene on a sex chromosome X-linked or Y-linked (X is larger so has more) Eye color in Drosophila an example: Cross red eyed female with a white eyed male All F1 red eyed flies F2 showed 3:1 ratio expected, but white eyed flies were all male

Gene Linkage Morgan’s research on fruit flies led him to principle of linkage Identified over 50 Drosophila genes Discovered many seemed “linked” in a way that violated independent assortment Ex.- reddish-orange eyes and miniature wings inherited together

Observed so many linked genes, Morgan could group them into 4 linkage groups Linkage groups assorted independently, but all genes in 1 group inherited together Drosophila has 4 linkage groups Also has 4 chromosomes

Two conclusions: -each chromosome is a group of linked genes -principle of independent assortment still holds true Chromosomes assort independently, not individual genes

Gene Maps Crossing-over sometimes separates and exchanges linked genes Produces new combinations of alleles Helps generate genetic diversity Can use rates of crossing-over events in meiosis to produce a gene map

Shows relative distances between genes on a chromosome Further apart two genes are, more likely they are to recombine (during crossing-over) Closer together, the less likely they are to become “unlinked”

Mutations Changes in the genetic material Germ-cell mutations occur in gametes Somatic mutations occur in body cells Lethal mutations cause death, often before birth Kinds of Mutations Changes in a single gene known as gene mutations Changes in a whole chromosome known as chromosomal mutations

Gene Mutations Mutation involving changes in one or a few nucleotides are called point mutations Include: Substitutions- one base changed to another Insertions- extra base inserted Deletions- base is removed from sequence

Substitutions usually only affect one amino acid in protein Insertions/deletions can affect whole protein Sequence read in codons (groups of 3) If base added or deleted, “shifts” the codons that are read Called frameshift mutations May change every amino acid after mutation

mRNA: AUG-CGU-ACC-UUA Amino acids: Met-Arg-Thr-Leu Substitution DNA: TAC-GCA-TGG-AAT mRNA: AUG-CGU-ACC-UUA Amino acids: Met-Arg-Thr-Leu Substitution DNA: TAC-GTA-TGG-AAT mRNA: AUG-CAU-ACC-UUA Amino acids: Met-His-Thr-Leu

mRNA: AUG-CGU-ACC-UUA Amino acids: Met-Arg-Thr-Leu Insertion DNA: TAC-GCA-TGG-AAT mRNA: AUG-CGU-ACC-UUA Amino acids: Met-Arg-Thr-Leu Insertion DNA: TAT-CGC-ATG-GAA-T mRNA: AUA-GCG-UAC-CUU-A Amino acids: Ile-Ala-Tyr-Leu

DNA: TAC-GCA-TGG-AAT-GGA mRNA: AUG-CGU-ACC-UUA-CCU Amino acids: Met-Arg-Thr-Leu-Pro Deletion DNA: TGC-ATG-GAA-TGG-A mRNA: ACG-UAC-CUU-ACC-U Amino acids: Thr-Tyr-Leu-Thr

Chapter 14- Human Genome Sickle Cell Anemia Common genetic disorder found in African Americans Have bent, twisted red blood cells Cells more rigid, tend to get stuck in capillaries Produces physical weakness and damage to brain, heart, and spleen

Chapter 14- Human Genome Protein affected is hemoglobin: Just one base change causes protein to be abnormal Abnormal protein causes sickle shape of cells Why so many African Americans? Tropical regions have high prevalence of malaria

Chapter 14- Human Genome People who are heterozygous normally healthy, and are resistant to malaria Sickle cell allele is beneficial in these areas A Mutation Story

Chromosomal Mutations Involve changes in the number or structure of chromosomes Can change locations of genes Can change the # of copies of some genes

Mutations that cause dramatic changes in protein structure or gene activity often harmful Mutations may produce proteins with new or altered activities that may be useful Mutations in gametes can be passed along to offspring Basis for new genetic variation in species

Studying Human Inheritance Human genes inherited according to Mendel’s principles Must identify an inherited trait is controlled by a single gene First, must establish trait is inherited Second, must study how trait is passed from generation to generation

Pedigree chart is used to show relationships within a family and follow a particular trait Genetic counselors analyze pedigrees to infer the genotypes of family members Only useful for single-gene traits Many human traits are polygenic Controlled by many genes Many traits also influenced by environmental factors

Recessive Alleles Many human genes become known through study of genetic disorders Most cases, presence of a normal gene only revealed when abnormal allele affects phenotype Autosomal recessive inheritance

Ex.- phenylketonuria (PKU) Lack enzyme needed to breakdown phenylalanine Can buildup in tissues in infants and cause mental retardation Caused by autosomal recessive allele on chromosome 12

Dominant Alleles If you have dominant allele for a genetic disorder, it will be expressed Ex.- Achondroplasia (form of dwarfism) Huntington’s disease Causes progressive loss of muscle control and mental function (begins in 30’s) Autosomal dominant inheritance

Multiple phenotypes from multiple alleles More common for multiple alleles to control a trait in a population Only two alleles of a gene can exist within the cell, multiple alleles for a single gene can be found within a population Blood Group Genes Human blood comes in variety of genetically determined blood groups Number of genes responsible, best known are ABO blood groups and Rh blood groups

Rh determined by single gene with two alleles Either positive (dominant allele) or negative ABO group more complicated Three alleles: IA, IB, and i IA & IB are codominant Alleles produce proteins on red blood cell surface i allele is recessive; no proteins produced

Polygenic Inheritance Traits that are determined through expression of two or more genes Polygenic traits show wide range of phenotypes Ex- eye color, skin color, height

Sex-linked Traits Traits controlled by genes found on the sex chromosomes Any recessive allele found on the X chromosome of a male will not be masked (there is no other X in males) X-linked dominant and Y-linked are very rare

Colorblindness 3 genes associated with color vision found on X chromosome In males, defective version of any of these produces colorblindness Most common form: red-green colorblindness; affects 1 in 10 males (U.S.) Among females: 1 in 100

Males have only one X chromosome So, all X-linked alleles are expressed in males (even if recessive) In females, must have two copies of recessive allele to express trait Pattern: Males show recessive trait more often Males pass along allele to daughters

Hemophilia Two important genes on X chromosome help control blood clotting Recessive allele in either may cause hemophilia (blood clotting protein missing) 1 in 10,000 males born with disorder (U.S.) Treated by injections of clotting protein

Duchenne Muscular Dystrophy Sex-linked disorder results in progressive weakening and loss of skeletal muscle 1 in 3000 males in U.S. Caused by defective version of gene that codes for muscle protein No treatment or cure to date

Chromosomal Disorders Mechanisms that separate chromosomes in meiosis work well; sometimes fail Most common error = nondisjunction Occurs when homologous chromosomes fail to separate Abnormal #’s of chromosomes in gametes may lead to genetic disorders

Down Syndrome Individual may be born with 3 copies of a chromosome (called trisomy) Most common form of trisomy is called Down Syndrome (Trisomy 21) ~1 in 800 born with Down Syndrome in U.S. Produces mild to severe mental retardation

Detecting Human Disorders Genetic screening or genetic counseling -May use a karyotype or pedigree Fetal cells obtained through an amniocentesis or chorionic villi sampling Genetic tests have been developed to take advantage of small differences in DNA