IV. Human Autosomal Genetic Diseases

Who cares about pea plants? Mendel’s pea plant studies led the way to the basic understanding of genetics (Three Laws of Heredity) These same principles (laws) apply to humans and Punnett squares can be used to determine the probability that a child will be born with a genetic disease.

Genetic Diseases Genetic diseases are caused by abnormalties in the genes or chromsomes. These genes are present in all body cells (somatic cells) and are present the person’s entire life.

Three types of genetic diseases: Autosomal gene diseases Sex-linked gene diseases Missing or extra chromosome diseases Most of the over 4,000 known genetic diseases are rare and may only affect 1 out of millions. Others are more common and may be carried by 1 out of 20 people.

Autosomal Diseases/Disorders Autosomes are all the chromosomes except X and Y (sex chromosomes) There are 22 pairs of autosomes (1 pair of sex chromosomes) Autosomal diseases are genetic diseases whose genes are found on the autosomes. Most autosomal diseases are recessive. If a person has just ONE recessive allele on that gene, they are considered to be a carrier.

Autosomal Traits Genes located on Autosomes control Autosomal traits and disorders. 2 Types of Traits: Autosomal Dominant Autosomal Recessive

Examples of Autosomal Diseases/Disorders

Cystic Fibrosis Autosomal recessive About 5% of the human population carries the gene This gene is found on chromosome 7. Causes a production of a protein that makes a person’s body produce unusually sticky, thick mucus No known cure for cystic fibrosis

Phenylketonuria Autosomal recessive Known as PKU The recessive gene is found on chromosome 12 This gene tells the body to make the enzyme phenylalanine hydroxylase Those with the recessive gene do not make this enzyme Without the enzyme, there is a build up of phenylalanine This build up affects the nervous system and causes brain damage.

PKU….Just FYI… PKU is treatable and diagnosed with a blood test All 50 states routinely test every newborn for PKU Treatment involves avoiding all proteins containing phenylalanine

Tay-Sachs Recessive autosomal disease Affects people of Eastern European Jewish descent more often than any other ethnic group Found on chromosome 15 This gene provides instructions for making part of an enzyme in lysosomes and helps break down a fatty substances. With the recessive gene, this fat isn’t broken down and starts to build up in nerve cells and the brain. These children rarely live past the age of 4

Huntington’s Disease Autosomal dominant disease Found on chromosome 4 This gene provides instructions for making a protein called huntingtin. Although the function of this protein is unknown, it appears to play an important role in nerve cells (neurons) in the brain. People with Huntington’s disease progressively lose muscle control and mental functions until death Symptoms don’t usually appear until around the age of 20 or later

Breast Cancer Autosomal Dominant disease BRCA1 and BRCA2 are called tumor suppressor genes, because they control cell growth. BRCA1 is located on chromosome 17, and BRCA2 on chromosome 13. Scientists believe BRCA1 and BRCA2 work by fixing damaged or broken DNA. Women who inherit a mutated copy of the BRCA1 or BRCA2 gene accumulate broken and deformed chromosomes, and therefore have a greater chance of accumulating mutations that will lead to uncontrolled cell growth and cancer

Breast Cancer Most people who develop breast or ovarian cancer have no history of the disease in their family. In fact, only 5 to 10 percent of all breast and ovarian cancers are caused by inherited genetic factors. These rare cases typically result from inherited mutations in either the BRCA1 or BRCA2 gene.

Breast Cancer High-risk families include those whose members carry a mutation in either the BRCA1 or BRCA2 gene. A child needs to inherit just one copy of the mutated gene to have an increased cancer risk. Children who have a parent with a BRCA1 or BRCA2 mutation have a 1 in 2 chance of inheriting the mutation. Just because a person inherits the defective gene does not mean he or she will develop cancer, but inheritance greatly increases the risk. Out of every 100 women who inherit a mutated BRCA1 or BRCA2 gene, as many as 60 will develop breast cancer by age 50; by age 70, approximately 80 will develop breast cancer

Breast Cancer A person with a strong family history of breast or ovarian cancer is a candidate for genetic screening. By analyzing a sample of the patient's blood, doctors can identify whether the person has inherited a BRCA1 or BRCA2 mutation. The test cannot tell if or when the person will develop breast or ovarian cancer; it can only tell if he or she is at risk because of the faulty gene.

Genetic Testing en-angelina-jolie-genetic-tests/ en-angelina-jolie-genetic-tests/

Practice A young couple has decided to start a family. David is 28 years old and has PKU. His wife Tracy is 25 years old and does not have PKU. However, her aunt and two grandparents did have PKU. What is the probability that David and Tracy will have a baby with PKU?

Complete a Punnett Square What is the probability their children will have PKU?

V. Sex Linked Traits

Sex-Linked Genes Remember Mendel’s Law of Independent Assortment?? What did it state?

Linked Traits Mendel wasn’t a dummy…his Law of Independent Assortment is true most of the time. But, there are exceptions. Remember, Mendel didn’t know about genes and chromosomes. The Law of Independent Assortment is true IF the genes are located on different chromsomes.

Linked Traits However, for genes on the same chromosome, they may be LINKED if they are close enough together on the same chromosome. If they are linked, they may be inherited together (not independently) The closer together the genes are on the chromosome, the more likely they are to be linked. For example, freckles and red hair seem to be linked

The Study of Linked Traits In the early 1900s, a scientist named Thomas Morgan and his graduate students were studying the fruit fly (Drosophila) They found that the fruit flies had several genes that did not show independent assortment He found that the flies that were gray tended to have long wings and the flies that were black tend to have vestigial wings

The Study of Linked Genes Morgan found that the genes that determine these traits are so close on the same chromosome that they tend to be inherited together. Many organisms, including humans, have linked genes.

Sex Chromosomes and Sex Linked Genes Humans have 23 pairs of chromosomes 22 pairs of autosomes; 1 pair of sex chromosomes The sex chromosomes are called the X and Y chromosome The X and Y chromosomes determine gender Females = XX Males = XY The X chromosome is larger and has more genes on it

What makes the Y different from X? There is a specific gene on the Y chromosome called the SRY gene. What the SRY gene does is start something called a gene cascade. This is sort of like an avalanche. The SRY gene turns on some boy making genes that turn on some more boy making genes and so on. Eventually you get a whole different set of genes working differently than they would without the SRY gene there.

What makes the Y male? One of the first genes that SRY turns on or activates is called SOX9. This gene is found on chromosome 17. This means boys and girls both have this gene. It is just that without SRY, it stays off. There are at least 5 other genes that come on early that have instructions for becoming a boy. They are located on different chromosomes like the X chromosome and chromosomes 9, 11, 17, and 19. Some of them are turned on by SRY or by genes like SOX9. This is actually how lots of things work in cells. Every cell has the potential to be a muscle, a blood cell, or any of the other hundreds of cell types. Cell type is determined by what genes are on and off.

Human Genome Project

Sex Linked Genes In humans, the X and Y chromosomes determine gender But they also have genes on them that determine other characteristics These genes are called sex linked genes because they are found on the sex chromosomes X and Y Because the X is larger and has more genes, most sex linked genes are on the X

Examples of Sex Linked Diseases/Disorders

Color Blindness Recessive trait Most common is red-green deficiency where a person has trouble telling the difference between red and green Both males and females can be color blind/color deficient but it is most common in males. –WHY??

Color Blindness The gene for color blindness is carried on the X chromosome Since it is recessive, it takes both recessive alleles on both X chromosomes for the person to have the deficiency A female would have to inherit the color blind allele from both of her parents

Color Blindness A male on the other hand, has only one X chromosome If he inherits the color blind gene from his mother on his X chromosome, he will automatically have the deficiency Why??? Because his father cannot give him the dominant gene for normal color vision because he gets a Y from his father (color blindness gene is only on the X)

Color Blindness Since it only takes the one recessive allele on the X chromosome for the male to be color blind, about 10% of males have some form of color deficiency

Hemophilia People with hemophilia do not have enough of the blood-clotting proteins and will bleed longer periods than normal The gene is carried on the X chromosome If affects more men than women but more women are carriers

Practice A color blind male marries a woman with normal vision. Use C to represent normal vision and c to represent color blind. Complete a Punnett square to determine the probability that their children will be color blind.