Human Genetics Chapter 14

Quick Chromosome Review What are chromosomes made of? DNA & PROTEINS When are chromosomes visible? CELL DIVISION What does it mean to be diploid? Have two sets of chromosomes One from mom & one from dad! Which cells are not diploid? Why? Gametes: haploid sperm (23) haploid egg (23) They must combine to form a diploid zygote (46)!

Sex Chromosomes Determine an individual’s gender Two chromosomes within the genome XX – Female All human eggs carry an X chromosome (23, X) X chromosome has > 1200 genes XY – Male About half of sperm cells carry an X, the other half carry a Y (23, X or 23, Y) Y chromosome is much smaller and has only about 140 genes mostly associated with male sex determination and sperm development

Autosomal Chromosomes Remaining 44 human chromosomes Humans have 46 total chromosomes 44 autosomal chromosomes (22 pairs) 2 sex chromosomes To correctly label a karyotype or summarize the number of chromosomes in a human cell: 46, XX (females); 46, XY (males)

Human Pedigrees Chart that shows relationships within a family Shows presence or absence of a trait and how it is passed on through a family used for any species used to infer genotypes of family members can determine if allele is dominant, recessive, autosomal, or sex-linked used to determine who in a family is at risk for genetic conditions by genetic researchers or counselors

Human Pedigree Children are placed from oldest  youngest Key explains what trait is!

ff Ff Ff Steps: Identify all people who have the trait. For the purpose of this class all traits will be given to you. In other instances, you would have to determine whether or not the trait is autosomal dominant, autosomal recessive, or sex-linked. In this example, all those who have the trait are homozygous recessive. Can you correctly identify all genotypes of this family? F- Normal f- cystic fibrosis Ff Key: affected male affected female unaffected male unaffected female

PKU P- Unaffected p- phenylketonuria Pp Pp Pp pp PP or Pp pp pp Pp Pp Key: affected male affected female unaffected male unaffected female

H-huntington’s disease h-Unaffected Key: affected male affected female unaffected male unaffected female

Sex-Linked Inheritance Colorblindness XCY XcXc XcY XCXc XcY XCXc XcY Key: affected male affected female unaffected male unaffected female

Karyotypes To look at the human genome, biologists photograph human chromosomes during mitosis (usually metaphase) Cut them out and arrange them into a picture called a karyotype Shows the complete diploid set of chromosomes grouped together in pairs Arranged in order of decreasing size

Normal Human Male (46, XY)

Normal Human Female (46, XX)

X Chromosome Inactivation Females have an extra X chromosome Most of genes in one of X chromosomes turned off Forms dense region in nucleus called a Barr body Same process in other mammals i.e. calico cats

Human Genetic Disorders Review: what is a mutation? Change in DNA sequence Changes proteins by altering amino acid sequence! Can directly affect the phenotype expressed! Many genetic disorders are caused by changes in an individual gene!

Sickle Cell Disease Caused by a defective allele for a protein in hemoglobin Causes hemoglobin molecules to stick together and form sickle shape More rigid and get stuck in capillaries Results in loss of blood flow and damage to cells, tissues, and organs

Cystic Fibrosis Known as CF Results from deletion of just three bases in gene for a protein called CFTR Protein is destroyed and doesn’t work as a transport protein, so proper ions aren’t transported across cell membrane Recessive trait – need two copies of defective allele for CF Serious digestive problems and thick, heavy mucus clogs lungs and breathing passageways

Huntington’s Disease Caused by dominant allele for a protein found in brain cells Mental deterioration, uncontrollable movements, appears in middle age Dominant, Autosomal

Genetic Advantages How do fatal alleles remain in the gene pool? Heterozygous individuals often show genetic advantages in certain situations Those heterozygous for sickle-cell are highly resistant to malaria Those heterozygous for CF had an advantage in medieval times and were resistant to Typhoid Fever

Chromosomal Disorders Errors can occur in meiosis Homologous chromosomes can fail to separate during Anaphase I Nondisjunction Results in gametes with an abnormal number of chromosomes Trisomy = 3 copies of a chromosome Down syndrome = Trisomy 21 Mild to severe mental retardation High frequency of birth defects

Male: 47, XY, +21 Female: 47, XX, +21 Trisomy 21

Sex Chromosome Disorders Klinefelter’s Syndrome, 47 XXY Turner’s Syndrome Nondisjunction of X chromosome Female inherits only one X chromosome Results in sterility and reproductive organs do not develop properly Klinefelter’s syndrome Males inherit extra X chromosome Interferes with meiosis and usually causes sterility No cases of babies born without X! Necessary for survival of embryo XXY

Human Genome Project Launched in 1990 Main goal: sequence 3 billion base pairs of human DNA and identify all human genes Completed in 2003 Completed genomes of many other organisms while working through human genome 40% of our proteins have strong similarity to proteins in many of those organisms (fruit fly, worms, yeast)

Human Genome Project Only about 2% of genome encodes instructions for synthesis of proteins Large areas of chromosomes with very few genes Pinpointed genes and associated particular sequences in those genes with diseases and disorders Identified about three million locations where single-base DNA differences occur in humans Help us find sequences associated with diabetes, cancer, and other health problems

HGP: What now? Ethical, legal, social issues Who owns and controls genetic information? How does genetic privacy relate to medical privacy? May 2008: Genetic Information Nondiscrimination Act Prohibits US insurance companies and employers from discriminating on basis of information derived from genetic tests Still don’t understand as many as 50% of the human genes thus far discovered