Inherited Diseases and Chromosomes Genetic diseases passed from parents to child before birth.

Autosome Chromosome Contagious Gene Genetic Material Heredity Karyotype Mutation Sex Chromosome TelomereCentromere Metaphase Zygote Tay-Sachs Hemophilia Cystic Fibrosis Huntingdon’s Disease Polycystic Kidney Disease AlleleExon Intron Transposon

Sickle Cell Anemia Autosomal Recessive –Males = 42 –Females = 48 –Oldest = 85

World Distribution One of the common misconceptions is that only black people get sickle cell, but this is not the case. There are many different ethnicities that can have sickle cell.

Who Can Get Sickle Cell? ANYONE can get Sickle Cell Disease. It is most common in the following ancestries: o African o Central or South American o Cuban o Indian o Saudi Arabian o Mediterranean o Hispanics ANYONE can get Sickle Cell Disease. It is most common in the following ancestries: o African o Central or South American o Cuban o Indian o Saudi Arabian o Mediterranean o Hispanics

Prevalence o It is estimated the up to 80,000 people in America have Sickle Cell Disease o 1/500 African Americans have Sickle Cell Disease o 1/ Hispanics have Sickle Cell o 1/12 African Americans are carriers for Sickle Cell o 1/50 Asians are carriers for Sickle Cell o 1/100 Greeks are carriers for Sickle Cell

It is Unknown why people with the Sickle Cell Trait are resistant to Malaria, but there are several theories… 1.The carriers of Sickle Cell have some abnormal Hemoglobin, and when they come in contact with the Malaria parasite they become sickled. Then those cells go through the spleen, which eliminates the cells because of their sickle shape, so the Malaria would be eliminated as well. 2.The Sickle Cell trait causes the malaria to stay in the body for an extended period of time, so it is able to build up a defense to it. 3.Because oxygen concentration is low in the spleen, and because infected cells often get trapped in the spleen, it is possible that they are destroyed in the spleen 4. The Malaria parasite produces an acid when it is inside of the red blood cells. This causes the red blood cells to polymerize, and the cells will sickle. These sickled cells are then destroyed when the blood cells go through the spleen.

Testing and Treatment Tests –Physical Exam –Blood Test –Pedigree –Electrophoresis Treatment –Bone Marrow Transplant –Stem Cell –Drug Therapy –Gene Therapy

Examples of Inherited Diseases Tay Sachs Hemophilia Cystic Fibrosis Huntington’s Disease Polycystic Kidney Disease Hemachromatosis Sickle Cell Disease

Tay Sachs What is it? A metabolic disease caused by the lack of an enzyme to efficiently breakdown fatty acid. 2:1 ratio of females to males. What is the outcome? Severe neurological disorders with death usually occurring before age 4. What are the symptoms? Loss of motor skills. Loss of muscle tone. Listlessness and Irritability.

Hemophilia What is it? A metabolic disease caused by the lack of a protein necessary to efficiently clot blood. What is the outcome? Prone to excessive bleeding, but modern drug therapy can lessen effect. What are the symptoms? Bruise easily. Blood slow to clot.

Cystic Fibrosis What is it? A disease caused by the production of abnormal, thick, sticky mucus. What is the outcome? Death caused by lung infections usually before age 35. What are the symptoms? Coughing and wheezing. Diarrhea. Chronic lung infections.

What is it?A progressive disease caused by the deterioration of nerve cells in the brain. What is the outcome? Continual decline in mental and physical ability; death usually occurs 15 to 20 years after onset. What are the symptoms? Difficulty walking. Uncontrollable body movements. Memory and cognitive impairment. Huntington’s Disease

Polycystic Kidney Disease What is it? A disease caused by the development of fluid-filled growths called cysts inside the kidney. What is the outcome? Dialysis or a kidney transplant may eventually be required. What are the symptoms? Blood in urine. Lower back pain. Kidney stones.

Hemachromatosis What is it?A metabolic disease caused by the over absorption of iron. What is the outcome? Damage to multiple organs due to excess iron. What are the symptoms? Joint pain. Fatigue. Heart problems.

Sickle Cell Disease What is it?A metabolic disease caused by the production of deformed hemoglobin. What is the outcome? Death in middle age due to increased risk of stroke, heart attack, and infection. What are the symptoms? Fatigue. Yellow colored skin—Jaundiced. Increased number of infections.

How Are Diseases Inherited? Passed from parent to child in the genetic material in the same way that all traits are passed to the next generation.

What Is Genetic Material? Genetic material refers to the chemical molecules that encode all the instructions cells need to function. These instructions are passed on to the next generation when cells reproduce. Reproductive cells carry the genetic material to create a new organism.

Human Reproductive Cells Egg: Produced by females in the ovary. Sperm: Produced by males in the testis. Both types of cells carry the genetic material needed to form a new human.

Egg Cell Used with permission Scott Kaplan, Pacific Fertility Center

Sperm Cells Used with permission of Sandra Caudle, Calhoun Community College

What Causes Inherited Diseases? Genetic material of a cell is changed causing a change in the cell’s and ultimately the body’s function which lead to a disease. The changed genetic material is passed from parents to child.

Reproductive Cells and Chromosomes Chromosomes contain the genetic material. Each reproductive cell contains one copy of each of the 23 human chromosomes.

Fertilization Sperm cell fuses with egg cell. The nucleus of the sperm cell is injected into the egg cell. After the sperm fertilizes the egg, a zygote containing 23 pairs of chromosomes is formed.

Early Zygote Used with the permission of Richard Sherbahn, MD. Advanced Fertility Center of Chicago Nuclei from egg and sperm fusing

What Are Chromosomes? Complex structures found in the nucleus of cells. Different types of organisms have different numbers of chromosomes. Number of chromosomes does not indicate complexity of the organism.

Number of Chromosomes in Cells from Different Animals Human46 Dog78 Cat38 Horse64 Cow60 Sheep54 Microsoft Office Clip Art

How Do Chromosomes Carry Information? Image courtesy of Dr. Sinnamon, Dean College of Arts and Sciences, Southern Wesleyan University

Chromosomes—What We Know Located in the cell’s nucleus. Humans have 23 pairs. Inherit one of each of the 23 types of chromosomes from each parent. Passed to new generation in sperm and egg cells. Inherited diseases are passed to new generation on chromosomes.

Chromosome Structure Each chromosome consists of a long single molecule of deoxyribonucleic acid (DNA). Basic chromosomal structure the same in all cells that contain a nucleus. –Including the cells that form plants, animals, and fungi

Chromosome Structure Exons –Specific nucleotide base sequence –Involved in producing proteins –DNA bases transcribed into mRNA and then amino acids Introns –DNA bases found between exons –Are not transcribed

Chromosome Structure Centromere –The constricted region of two sister chromatids. Teleomere –The end of the chromosome –Made of a reoccurring 6 nucleotide bases TTAGGG

Chromosome Function Contains the code or instructions for how to make specific proteins which then determine the organism’s traits. The specific instructions for a protein are on sections of the chromosome called genes.

What is a gene? A section of DNA that corresponds to a discreet unit of heredity (traits such as hair color). –Generally a gene is the information needed to make a specific polypeptide (chain of amino acids). –Proteins that are a single polypeptide are usually associated with a single gene. –Proteins that consist of multiple polypeptides are associated with multiple genes.

Jumping Genes? Transposons are called jumping genes. Sequence of DNA that jumps around within the chromosome. Can move, multiply, and mutate to alter the genome and DNA.

Which are more, genes or transposons? Genes –28 Transposons –500

DNA structure? 8 histone protein subunits attach to DNA to form a NUCLEOSOME 6 nucleosomes stack on top of each other. This creates a chromatin. 6 feet of DNA will fit into a nucleus.

U.S. Department of Energy Human Genome Program,

What is the relationship? A gene is a segment of the chromosome that codes for a single protein. A gene is a sequence in a DNA strand. A chromosome is composed of a single piece of DNA that contains genes.

Question What percentage of the human genome is identical between individuals? – 99.9%

How are you different from your friends? Single nucleotide polymorphism (or SNP) –Sites along the genome where individuals differ by a single base pair. –Multiple SNPs found throughout the three million DNA base sequence.

Sex Linked Traits Genes on the X chromosome are called “sex-linked”, because they expressed more often in males than in females There are very few genes on the Y chromosome. Since males only have one X chromosome, all genes on it, whether dominant or recessive, are expressed. In contrast, a mutant gene on an X chromosome in a female is usually covered up by the normal allele on the other X. Most mutations are recessive. So, most people with sex-linked genetic conditions are male. Another fact about sex-linked genes. Males produce ½ their sperm with their X chromosome, and half with their Y chromosome. The X- bearing sperm lead to daughters and the Y-bearing sperm lead to sons. So, sons get their only X from their mothers, and the father’s X goes only to daughters. The Y chromosome is passed from father to son.

X-linked Inheritance – When Men and Woman Play by Different Rules Behind the 8-ball? Colorblindness is an X-linked recessive trait.

A Boy with Cri-du-Chat Syndrome – a Debilitating Disorder Caused by Chromosome Deletion

Translocations Lead to a Number of Human Cancers In Burkitt’s lymphoma, a chromosome translocation causes a cell cycle-promoting gene to always be active.

Searching for Chromosomal Defects - Amniocentesis and Chorionic Villus Sampling Many new techniques for learning about individual genes rather than whole chromosomes are available or under development.

Searching for Chromosome and Gene Defects – Pre-Implantation Genetic Diagnosis (PGD) Removing a cell for diagnosis from a human embryo. The diagnosis: trisomy 21 (Down syndrome).

Chromosomes and Sickle Cell Chromosome 11 carries the instructions (genes) to make the hemoglobin protein. There are different versions of these genes: –Normal--healthy –Mutated or changed--Sickle cell or other hemoglobin disorder.

Activity Create chromosome spreads using human cells taken from a cancerous tumor. Observe the number and shapes of chromosomes in the spreads. Calculate the average number of chromosomes per cell.

AutosomeA chromosome that is not directly involved in determining sex, as opposed to a sex chromosome. ChromosomeAny of the usually linear bodies in the cell nucleus that contain the genetic material. ContagiousCapable of being transmitted from person to person, animal to animal, animal to human, or human to animal by contact. GeneA discrete unit of hereditary information. Genetic MaterialMolecules responsible for heredity and variation of organisms. HeredityThe transmission of traits from ancestor to descendant. KaryotypeA display of the chromosome pairs of a cell arranged by size and shape. MutationA rare change in the genetic material, ultimately creating genetic diversity. Sex Chromosome One of the pair of chromosomes responsible for determining the sex of an individual.