Human Bio Chapter 21

Genes

They are units of heredity, carried in DNA, and code for protein synthesis.

Genotype

Genes we inherited from our parents. We get two copies, one from our mom and one from our dad. Alleles are variations of genes, like eye color. Dominant alleles just need one to be expressed. Recessive alleles are only expressed in the absence of dominant alleles. Different genotypes are homozygous, is where you inherit the same allele. Heterozygous is where the two alleles are different. Genotype determines the phenotype, what is observed on the outside.

Gametes

Have 23 chromosomes and are considered haploid. Diversity of gametes are created through crossing over, where homologous chromosomes exchange genetic material. This makes the chromosomes more varied with a mixture of maternal and paternal genes. Random alignment or independent assortment is in metaphase I, where homologous pairs randomly line up down the center of the metaphase plate. Some chromosomes end up on the left and right side randomly, increasing diversity. Gametes combine to form a zygote, when sperm fertilizes an oocyte and the resulting diploid cell starts developing (46 chromosomes). 23 were from the sperm and 23 were form the egg. This is sexual reproduction, providing more diversity in the species. Diversity decreases the likelihood of genetic disorders. When genes combine, it is called a cross where genes combine to make a genotype.

Single Trait Crosses

Also called monohybrid crosses. The dominant gene is a capital letter like Freckles (F). Recessive is no freckles (f). If someone inherited a copy of the dominant gene, they will display freckles. However, if someone inherited two copies of the recessive, they would have no freckles. Possible genotypes are FF or Ff (homo and heterozygous) which provide freckles. The genotype for no freckles is ff because it is recessive. With the dominant phenotype, it is either homozygous dominant or heterozygous. If the parents both have ff, then the zygote will have ff as well and will be homozygous recessive. The phenotype is freckles if at least one of the parents has dominant allele F and the zygote inherits it.

Two Trait Crosses

Dihybrid cross. Examples are freckles and finger length. Dominant is freckles and short fingers (F and S) and recessive is no freckles and long fingers (f and s). Combining these, the possible genotypes are FFSS, FFSs, FfSS, FfSs for freckles and short fingers. FFss and Ffss for freckles and long fingers. ffSS and ffSs for no freckles and short fingers. ffss for no freckles and long fingers. 100% of the time, 16/16 will have freckles with short fingers. With a cross between homozygous dominant and homozygous recessive, 100% of the time the zygote will be heterozygous but display the dominant phenotype. With two heterozygous phenotypes, it turns out there is a lot more diversity when you cross them.

Patterns of Inheritance

You can have autosomal inheritance, which is chromosomes 1-22. This is different from the sex chromosomes, which are the 23rd pair of chromosomes (XX or XY). A genetic disorder or genetic trait can be inherited through autosomal dominant, and you only need to inherit a single copy of that gene on the autosome to get the disorder. If it is autosomal recessive, you need two copies of the allele in order to get the disorder. X-linked disorders are carried on the X chromosome. An X-linked dominant condition means that you only need one copy of that gene to inherit the trait. X-linked recessive means you need two copies of the allele to inherit the trait. Y-linked is dominant because a male only has one Y, so it will always be expressed if present.

Pedigrees

Scientists can create these based on your family and analyze them to give insight into the pattern of inheritance of a trait. Circles are females and squares are males. The colored in shapes are the people affected by the trait. Horizontal lines mean mating, and vertical lines mean offspring.

Autosomal Dominant

This means that the dominant gene is on an autosome (1-22 pairs) and you only need a single copy of the mutated/defective gene to express the trait. The genotype can either be homozygous dominant or heterozygous. Two affected parents can produce an unaffected child. Two unaffected parents cannot have an affected child, because the child needs to inherit the dominant gene from one of the parents. If they are both healthy and homozygous recessive, they cannot have an affected child who is heterozygous or homozygous dominant. Affected children must have at least one affected parent. Heterozygotes are affected. Males and females are affected with equal frequency because it is not sex chromosome linked.

Autosomal Dominant Examples: Marfan Syndrome

This is a genetic disorder involving a protein called fibrillin. The gene for this elastic protein is mutated, so the connective tissue of people with this disorder lacks elasticity. There is sever nearsightedness of the eyes, curvature of the spine (scoliosis) and a caved in chest. The arteries can also weaken and cause aortic dissection and aortic ruptures, leading to instant death. People with the disorder must be closely monitored by their doctor to make sure the aorta is not dilating. If there are effects on the aorta, it can be replaced with synthetic elastic tissue through surgery.

Autosomal Dominant Examples: Osteogenesis Imperfecta

This disorder involves a gene for protein collagen type 1, which is a very strong protein found in connective tissues like bone. It creates the strength and bendiness of living bone. People with the disorder do not make collagen type 1, so their bones are brittle and they end up having frequent fractures. It can be fatal in the most severe types, but in the less severe one, it is a chronic problem of constant fractures.

Autosomal Dominant Examples: Huntington Disease

A progressive neurodegenerative disorder caused by a mutation in a protein and a mutation in a gene for a protein called Huntington. You end up developing abnormal cells in the brain. The neurons have changed shapes and form clumps, causing them to die off. Dark proteins form and there are fewer neurons in general. The phenotype of Huntington’s is dementia, and progressively it gets worse until all mental faculties are gone and there’s a loss of control of bodily function. The disease’s symptoms only arise in your mid 30s to 40s, meaning you potentially passed the gene on to your offspring if you reproduced. This disease progresses very quickly, meaning that you may die within 10 to 15 years. If you have a family history of the disorders, you can be tested for it. Because it is autosomal dominant, if you are heterozygous there is a 50% chance of passing it on to your children. After testing to see if you have it, you can choose not to have offspring or there are ways to prevent the offspring from inheriting the defective gene.

Autosomal Recessive

This gene would be on an autosome, and you need to inherit two copies of the defective gene in order to have the disorder. The genotype is aa, and affected children can have unaffected parents. Two affected parents will always have an affected child because they are homozygous. Heterozygotes are unaffected and are called carriers without expressing the gene.

Autosomal Recessive Examples: Tay-Sachs Disease

There is a lack of a lysozyme enzyme called Hex A. This enzyme’s job is to get rid of fatty acid proteins which build up in the brain. The disorder would make lysosomes malformed, and they clean out fats and proteins without getting rid of them. Over time, the bulge of the lysosomes will cause damage and cell death to the neuron. Symptoms are blindness, seizures, paralysis, and eventual death. Children affected by this would often die by the age of five.

Autosomal Recessive Examples: Cystic Fibrosis

This disorder is caused by a defective chloride ion channel. In the case of this disorder, the ion channel is 100% ineffective or partially ineffective. Because of this, there is a buildup of chloride, which causes a buildup of water. On the other side of the membrane, there is a buildup of sticky mucus. Patients with the disorder experience frequent lung infections because of mucus buildup within the lungs. They suffer digestive problems because the ducts and tubes like the pancreatic one clog with mucus. They also tend to be infertile because the gametes are unable to move through the uterine tube or male reproductive ducts. Life expectancy is 20-40 and there are 1500 different mutation for the disorder. Delta F508 is very severe, and other ones are less severe. The more severe the mutation, the more fatal the condition.

Autosomal Recessive Examples: Sickle-Cell Disease

This disease results from a gene which causes an abnormal form of hemoglobin to be created. When hemoglobin carries oxygen or not, it is in a globular form. With this disease, when the hemoglobin is lacking oxygen, it becomes spear shaped so the cell becomes sickle shaped (crescent moon). The cells get trapped in small blood vessels and cause small emboli or blood clots. People who are in a sickle cell crisis when they’re exposed to low oxygen levels or when they’re exerting themselves/stressing their bodies, they end up having joint and muscle pain because the vessels supplying those organs are occluded by the small emboli. Other things that happen with sickle cell disease is anemia. Sickle shaped cells are removed by the body from the spleen and liver, leading to a drop in blood cell count: anemia.

X-linked Recessive

The gene is carried on the X chromosome, and you have to inherit only recessive genes to inherit this disorder. For X-linked alleles, XAXA is a healthy female, XAXa is a heterozygous carrier female, and XaXa is an affected female, homozygous recessive. For males, XAY would be a healthy male, and XaY is an affected male. Because males only have one X, there is no homozygous or heterozygous with their genotype. We have to consider the allele and the sex chromosome in Punnett squares. Affected genotypes include homozygous recessive females and recessive males. Males are more affected because they only have one X. The trait tends to skip a generation, and an affected son can have parents that are unaffected and affected. Affected mothers will always have affected sons because sons always inherit their X from their mother. An affected daughter must have an affected father and at least a carrier mother.

X-Linked Recessive Examples: Color blindness

You are lacking a gene for one or more of the cones photoreceptors. This creates a blindness to certain colors, especially on the X chromosome. The gene for the red and green cones are not as sensitive, so the person cannot see reds or greens if they have X-linked recessive color blindness. Images would have a grayish tone to them.

X-Linked Recessive Examples: Duchenne Muscular Dystrophy

The gene for this is found on the X chromosome, and it codes for a protein called dystrophin. Dystrophin is a protein that stabilizes the membrane of your muscle cells. When the protein is defective or nonexistent, the membranes of our muscle cells become very weak and susceptible to injury. When it is damaged, it becomes scar tissue which cannot contract and generate force. As muscles get used, over time the cells get replaced by scar tissue and paralysis occurs. Children begin as mobile but slowly become paralyzed as they use their muscles. They end up in wheelchairs then ventilators, and typical lifespan is until 20-25. There is no cure for this kind of dystrophy.

X-Linked Recessive Examples: Fragile X Syndrome

This is the most common cause of inherited mental impairment, and is one of the causes of autism. A person with this syndrome has a mutation in the gene that codes for a protein called fragile X mental retardation protein. This protein is necessary for proper brain development, so this is why this disorder results in mental impairment.

X-Linked Recessive Examples: Hemophilia

It is a bleeding disorder where blood clotting is not able to occur or does not occur fast enough or efficiently enough to stop bleeding. X-linked hemophilia is due to a mutation in a gene for a clotting factor. Clotting factors are inactive proteins that exist in our blood, but when our vessels become compromised, those clotting factors become active to form a fibrin clot. Two clotting factors, clotting factor eight and nine are most affected by X-linked hemophilia.

Polygenic Inheritance

Multiple genes are involved, possibly multiple chromosomes as well. The effects are additive, so if the genes alleles are more dominantly, the more dominant phenotype is expressed. If the recessive alleles are inherited, the more recessive the phenotype expressed. This kind of inheritance also demonstrates continuous variation. The variation is directly proportional to the number of genes involved. For example, height is a polygenic trait, so if we plotted height and number of people in height ranges, most people fall within a middle range of 66-70 inches. This is different from single trait inheritance, which has no variation: you either have the trait or you don’t.

Multifactorial Inheritance

This type of inheritance is polygenes and the environment affecting those genes. Examples of humans is the cleft lip and palate can come simply from genetics, but also from malnourishment or low vitamin intake. Clubfoot is a genetic predisposition which can be exacerbated by poor nutrition. People with diabetes have a genetic predisposition for it, especially type II. They can develop diabetes more easily if they make lifestyle choices such as low exercise and having high fat and high sugar diets. Cancer is a multifactorial trait as well. There are genes in your cells which will turn cancer off or prevent cancer, and others which turn cancer on. When those genes are mutated or activated, depending on the specific gene in combination with environmental factors (nutrition, stress, age, toxin exposure) can tip the scales for developing cancer. People have a genetic predisposition for allergies, and when they are immunocompromised it becomes worse. When you are exposed to certain environmental allergens, you express that trait of having allergies. If a person has the predisposition to be allergic to a plant but is never exposed to it, they will not have an allergic reaction. However, once they are exposed, their allergy will flare up.

Pleiotropy

Another form of more advanced genetic inheritance. This is when1 gene affects 2 or more traits. An example is Marfan syndrome, an autosomal dominant disorder resulting from a gene that codes for the protein fibrillin. This protein is necessary to stabilize the elasticity of our connective tissues. If the gene is expressed in the different tissues, there are effects on the skeleton all over. There are physical deformities, and ones on the heart and blood vessels. The single gene that codes for fibrillin can affect all these different tissues, which is what makes it pleiotropy.

Incomplete Dominanace

A form of advanced inheritance where heterozygotes have an intermediate phenotype. Examples are that curly hair and straight hair mate and have a child with an in between: wavy hair. Familial hypercholesterolemia is a genetic cause of high blood cholesterol, and the disorder affects the number of LDL (bad cholesterol) receptors. With a reduced level of these receptors, cholesterol ends up getting deposited under the skin, especially in the limbs. If you are homozygous for the genetic disorder, you would have very high levels of cholesterol. If you are heterozygous for the disorder, you would have an intermediate level of cholesterol. Symptoms in the joints are swellings or lumps.

Co-Dominance

Two alleles of a heterozygote are equally expressed through the phenotype because they are both dominant. If you inherit one copy of A and one of B, the phenotype will be AB because both alleles are dominant.

Multiple Allele Inheritance

This happens when there are more than two alleles. This means that more than three possible genotypes result. For example, the ABO blood system has the possible alleles of A, B, and O. The possible genotypes are AA, AO (phenotype A), BB, BO (phenotype B), AB (phenotype AB), and OO (phenotype O). With single allele inheritance, there are three different genotypes, and two different phenotypes. However, with more than 2 alleles, there are six different genotypes and four different phenotypes.