Chapter 12 Human Genetics Modern Study of Genetics • 1882: Flemming observed threadlike chromosomes in the nuclei of dividing cells • 1887: Weismann suggested that meiosis halves the number of chromosomes when gametes are made – 1900 Mendel work was finally appreciated especially his view that diploid cells have two units for the trait – units segregate during gamete formation Chromosomes and Inheritance • Genes are units of information about inheritable traits • Diploid organisms possess pair of homologous chromosomes, which are alike in length, shape, and gene sequence • Alleles are slightly different molecular forms of the same gene, which are suffled during meiosis Continue… • Crossing over between chromosomes results in genetic recombination • Independent assortment: refers to the random alignment of each pair of homologous chromosomes at metaphaseI of meiosis , which results in new combinations of genes in offspring • Chromosome’s structure may change during mitosis or meiosis Section 12.2 • You will have questions on your test – be sure you go back and look at that section Sex Determination • Each human egg will contain 22 autosome plus one X but sperm will carry 22 autosomes plus either an X or Y – X bearing Egg plus X bearing sperm produces female offspring – X bearing egg plus Y bearing sperm produces male offspring Continue… • X Chromosomes obviously codes for sexual traits, but it also carries many genes for nonsexual traits – Y chromosomes carries a male determining (SRY) gene which leads to formation of the testes – Absence of the male gene in females results in formation of ovaries Linked genes • Linked genes on specific chromosomes are referred to as linkage group • Thomas Hunt Morgan: fruit flies experiment confirmed the location on a chromosome – Some of the most intriguing linkage are those of X-linked and Y-linked genes • Analysis lead to the result of linkage groups and gene locations Human Genetics • Is very difficult to study – We live in very diverse population and variable conditions – Mate by chance and may or may not choose to reproduce – Small family size is not sufficient for meaningful statistical analysis Pedigrees • A pedigree is a chart that shows genetic connections among individuals • Provides data on inheritance patterns through several generations • Knowledge of probability and Mendelian inheritance patterns is used in analysis of pedigrees to yield clues to a trait genetic basis Human Genetic Disorder • Genetic abnormality- is a condition that is deviation from the usual, or average and is not life threatening • Genetic disorder- is more appropriately used to describe conditions that cuase medical problems • Genetic disease- applied to those instances where a person’s genes increase susceptibility to infection or weakens the response to it. Autosome • any chromosome other than the X & Y (humans have 22 pairs of autosome + 1 pair of sex chromosomes) Autosomal Recessive Inheritance • Characteristics of this condition are: – Either parent can carry the recessive allele on an autosome – Heterozygotes are symptom-free – Homozygous are affected – 2 Heterozygous parents • 50% producing a heterozygous child • 25% homozygous recessive • Galactosemia (inability to metabolize lactose) – Single gene mutations prevents the manufacturing of an enzyme needed in the conversion pathyway Autosomal Recessive Examples of Autosomal Recessive • • • • • • • • • Tay - Sachs Disease More common among Jewish populations Young children begin showing signs of slowed development Severe impairment and death Cystic Fibrosis More common in Caucasion Mucus in respiratory tract, difficulty breathing extreme salty sweat Mucus may cause secondary infections • • • • • • • • • • Phenylketonuria (PKU) Lack enzyme for normal metabolism Phenylalanine builds up and causes brain damage Newborns are routinely tested Changes in diet lead to normal life Sickle Cell Disease More common in Africans (African-Americans) Causes blood to be sickle shaped Affects oxygen flow to organs, causing weakness, pain, anemia, etc Heterozygotes are resistant to malaria Autosomal Dominant Inheritiance • The dominant allele is nearly always expressed and if it reduces the chance of surviving or reproducing, its frequency should decrease; nonreproductive effects, and postreproductive. • If a parent is heterozygous and other parent is homozgyous recessive there is a 50% chance that any child will be heterozygous Autosomal Dominant Examples • Neurofibromatosis • Tumors form under skin and • Can cause skeletal deformities, blindness • Huntington Disease • Neurological disorder, progressive degeneration of the brain • Symptoms appear later in life • Achondroplasia • Common form of Dwarfism • Short arms and legs, normal torso • Homozygotes (AA) do not survive Examples • Huntington Disease: serious degeneration of the nervous system with an onset from age 40 onward, which time the gene has usually been passed on to offspring • Achondroplasia (dwarfism) Benign abnormality that does not affect the person reproductively X-linked Recessive Inheritance • Characteristics of this condition are – Mutated gene only on the X chromosome – Males: are either normal or afflicted – Female: can be normal, carrier, and afflicted • Examples: – Hemophilia A having the inability to clot blood – Fragile X syndrome defective X chromosomes that produces a faulty protein that results in retarded brain development Continue… • Some genes are located on the X chromosome. Females receive two alleles for these genes, but males only receive one. • When doing a punnet square, use large X's and Y's to denote male and female, use superscript letters to designate the alleles • If you are trying to determine if an allele is sexlinked, and which is dominant, a reciprocal cross is performed White eyed male x red eyed female | Red eyed male x white eyed female • XrY x XRXR | XRY x XrXr Human Sex-Linked Disorder • Colorblindness • Red-green colorblindness makes it difficult for the person to discern the two colors (test yourself!) • If the parent is a male, the genotype is automatically known. A colorblind male has to be b, since he only has one allele and colorblindness is recessive. A normal male must then be B • Females can be heterozygous for the colorblindness trait - they are called carriers. A female can be BB normal, Bb - carrier, or bb - colorblind • The following shows a cross between a normal man and a woman who is a carrier. Continue… • Muscular Dystrophy • characterized by the wasting away of muscles • life expectancy: ~20 yrs • females can be carriers for the disease, where they pass the disease to their sons only • Hemophilia • also known as "bleeder's disease" • blood does not clot properly • disease was present in the royal family, starting with Queen Victoria Continue… • Fragile X Syndrome • caused by triplet repeats in a gene on the X chromosome • causes mental retardation • named because the X chromosome had an odd appearance - the tip of the chromosome seemed to be attached only by a small thread • the number of repeats of the gene determines the severity of the disease Problems: • Problems: 1. What is the chance that a woman with hemophilia will have a child with hemophilia? (What sex would the child need to be?) • 2. In a cross where a brown-haired female is crossed with a black-haired male, all the male offspring have brown hair and all the female offspring have black hair. What must be the genotypes of the parents? Which allele is dominant? • Continue Problems…. • 3. In drosophila (fruit fly), the allele for eye color is located on the X chromosome, where red eyes is dominant to white eyes. Show the cross of a heterozygous redeyed female and a white eyed male. • 4. A man who is colorblind marries a woman whose father is colorblind. What is the chance that they will have colorblind children? Progeria • Read Focus on Health • A genetic disorder in which a individual rapidly ages Karyotype A picture of a person's chromosomes, arranged by size and grouped into homologous pairs. Chromosomes Changes • Duplication: when a gene sequence is in excess of the normal amount; apparently this true region that code for polypeptides of hemoglobin and is not harmful Chromosomes Changes • Inversion: alters the position and sequence of the genes so that gene order is reversed Chromosomes Changes • Translocation: occurs when a part of one chromosome transferred to a nonhomlogous chromosome – Leukemia in which segment number 9 is attached to chromosome 22 Chromosomes Changes • Deletion: is loss of a chromosome segment as when a terminal segment is lost or when viruses, chemical or irradiation cause breaks in a chromosome region Example: Cri-du-chat (deletion of chromosome of 5 Changes in Chromosome Number • Aneuploidy is a condition in which the gametes or cells of an affected individual end up with one extra or one less chromosome than is normal Continue.. • Polyploidy is the presence of three or more of each type of chromosome in gametes or cells – Common in plants but fatal in humans • A chromosome number can change during mitotic or meiotic cell division or during the fertilization process • Tetraploid germ cells can result if cytoplasmic division does not follow normal DNA replication or mitosis Nondisjunction • At anaphase I or anaphase II frequently results in a change in chromosome number – If gamete with an extra chromosome (n+1) joins a normal gamete at fertilization the diploid cell will be 2n+1, this condition is called trisomy – If an abnormal gamete is missing a chromosome, the zygote will be 2n -1 monosomy Down Syndrome • Down syndrome results from trisomy 21 – 1 in 1,100 liveborns in North America are affected – Mental Retardation – Heart Defects – Frequently occur with women over the age of 35 Changes in Sex Chromosomes Females • Turner Syndrome – Whose cells have only one X chromosomes (XO) – Infertile – Shorter life expectancy – Premature aging – 75% of the cases are due to nondisjunction in the father Changes in Sex Chromosomes Females • XXX Condition – Females inherits 3, 4, or 5 chromosomes – Girls are taller and slimmer than average – Fertile – Fall in the normal range of appearance and social behavior Changes in Sex Chromosomes Males • Klinefelter Syndrome – Nondisjunction results of an extra X chromosome (XXY) – 67% results from a nondisjunction in the mother – Sterile – Slight Mental Retardation – Body Feminization Changes in Sex Chromosomes Males • XYY – Extra Y chromosome in these males – Fertile – Taller than average – Slightly mental retarded – Erroneous correlation have linked these persons with predisposition to crime