Genetic Disorders & Sex Linked Traits Honors Biology Unit 5 2012-2013 Recessive Disorders Disorders that are only expressed in the phenotype when 2 recessive alleles are present. DD = Normal Dd = Carrier dd = Affected by disorder 2 Examples of Recessive Disorders Tay-Sachs Disease A genetically caused disease in which the gene to make the enzyme Hex-A (Hexosaminidase A) is not working. Hex-A is an enzyme that breaks down the lipid GM2 ganglioside. Without Hex-A this lipid accumulates on nerve cells, specifically in the brain causing severe brain damage. Victims of this disease to not live past age 5 Common in Eastern European Ashkenazi Jews This is a group of people descendent of medieval Jews from the Rhineland area. (Rhineland: near the river Rhine in Germany) Common in this population (1 in 30) Tay-Sachs Brain How is Tay-Sachs disease passed? Each parent must be a Carrier Offspring: 25% Normal 50% Carriers 25% Tay-Sachs Cystic Fibrosis Thick mucus is produced by the body Mucus fills lungs causing lung infections Mucus blocks pancreas which causes digestive problems Mucus can block bile ducts in liver causing liver failure. Cystic Fibrosis Cystic Fibrosis Most common in Caucasian (white) populations (1 in 2500 to 3500) 1 in 17,000 African Americans 1 in 31,000 Asian Americans Carriers of Cystic Fibrosis Offspring: 25% Normal 50% Carriers 25% Cystic Fibrosis Dominant Disorders Disorders that are expressed in the phenotype of heterozygous and homozygous dominant individuals DD = Affected Dd = Affected dd = Normal 2 Examples 1) Huntington’s Disease Brain cells degenerate over time Mood swings, loss of muscle control, loss of memory and inability to learn, death. Usually adult-onset, appears around ages 40-50 Outlook is 10-15 years of survivablity hh = Normal HH or Hh = will get and die of this disease Person with Huntington’s and a person without Huntington’s Hh x hh Offspring: 50% Huntington’s 50% Normal Huntington’s is most common in certain parts of Venezuela (700 in 100,000) Generally affect 3-7 in 100,000 of European ancestry Less common in African-American & Asian American 2) Marfan’s Syndrome Defective gene for fibrillin-1 that results in abnormal connective tissue Aorta may stretch or become weak, causing aortic rupture, the leading cause of death Eye/lens problems Excessive long bone growth (long arms & fingers) Hypermobile joints (too flexible) Chromosome Structure Variations Chromosomes can be broken by X-rays and by certain chemicals. The broken ends spontaneously rejoin, but if there are multiple breaks, the ends join at random. This leads to alterations in chromosome structure. Breaking the chromosome often means breaking a gene. Since most genes are necessary for life, many chromosome breaks are lethal or cause serious defects. Also, chromosomes with structural variations often have trouble going through meiosis, giving embryos with missing or extra large regions of the chromosomes. Chromosome Structure Variations The major categories: duplication (an extra copy of a region of chromosome) deletion (missing a region of chromosome) inversion (part of the chromosome is inserted backwards) translocation (two different chromosomes switch pieces). Chromosome Variations Changes in number and structure are possible: first look at number variations. Aneuploidy: having an extra or missing chromosome– is fairly common in sperm and eggs. Errors in meiosis causes chromosomes to not separate equally into the gametes. The rate of aneuploidy in males is constant: 1-2% of sperm have an extra or missing chromosome. Chromosome Variations In females, the rate increases with age. This is illustrated by the frequency of Down syndrome births at different ages of mother. Down syndrome is the most frequent result of aneuploidy. Chromosome Number Variations: Aneuploidy Except for the X and Y, humans don’t survive with only 1 copy of any chromosome. Also, 3 copies is lethal in most cases. Aneuploidy is a major cause of spontaneous abortion in early pregnancy. Down Syndrome is the most common human aneuploidy. It is also called trisomy-21, meaning 3 copies of chromosome number 21. Trisomy: *Having 3 chromosomes of each kind instead of 2 *Normally trisomy results in death. 1 Example Down Syndrome: a genetic condition in which the individual has 3 copies of the 21st chromosome. Genotype: 3 copies of 21st chromosome Down Syndrome: Phenotype: People with Down’s have a characteristic appearance: flattened face, turned up nose, epicanthal folds at the outer corners of the eyes. In most cases the diagnosis is made immediately at birth. Heart defects, protruding tongue, and mental retardation are also found in most people with Down’s. Occurs about 1 in 1000 births. Sex Linked Traits Sex Linked Traits Traits that occur on the X or Y chromosome X-linked traits are traits found on the X Chromosome Sex-linked Genes 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. Sex-linked Genes 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. Why can females have 2 copies of the X chromosome, when 2 copies of most chromosomes is deadly? Answer: In each cell one of the X chromosomes ‘turns off’. This turned off chromosome is known as a Barr body. The effect of Barr bodies can be seen in Calico colored cats. Why can females have 2 copies of the X chromosome, when 2 copies of most chromosomes is deadly? Example: Calico Colored cats. A calico cat has patches of orange and patches of black X = orange X1 = black Males: XY = orange / X1Y = black Females: XX = orange / X1X1 = black / XX1 = calico Because individual cells determine which X chromosome to deactivate, the patches of color arise Colorblindness We have 3 color receptors in the retinas of our eyes. They respond best to red, green, and blue light. Each receptor is made by a gene. The blue receptor is on an autosome, while the red and green receptors are on the X chromosome (sex-linked). Colorblindness Most colorblind people are males, who have mutated, inactive versions of either the red or the green (sometimes both) color receptors. Most females with a mutant receptor gene are heterozygous: the normal version of the receptor genes gives them normal color vision. Colorblind Test! You will see circles with many colors of dots The dot pattern makes up a number What number do you see? With Color Vision: This one you can even see in black and white Color Blind Test What number do you see? Color Blind Test What number do you see? This what you would see if you were color blind What number do you see? Color Blind Test What number do you see? Color Blind Test What number do you see? Color Blind Test What number do you see? Color Blind Test What number do you see? With color vision you see this: But if you were red-green colorblind…. You would see the #: 5 What do the colorblind see? Types of Colorblindness NORMAL RED YELLOW GREEN CYAN BLUE MAGENTA PROTAN: DEUTERAN: TRITAN: Red Blind Green Blind Blue Blind Types of Colorblindness – Normal Protanopia: no red No color vision Deuteranopia: no green Tritanopia: no blue How to write Alleles for X-Linked Traits Women: Normal: XBXB Carrier: XBXb Colorblind: XbXb Men: Normal: XBY Colorblind: XbY Hemophilia Hemophilia is a disease in which the blood does not clot when exposed to air. People with hemophilia can easily bleed to death from very minor wounds. Hemophilia is another sex-linked trait. Hemophilia is treated by injecting the proper clotting proteins, isolated from the blood of normal people. In the early 1980’s, the blood supply was contaminated by HIV, the AIDS virus, and many hemophiliacs contracted AIDS at that time. Small cuts, scrapes and bruises can be life threatening 1 in 10, 000 males 1 in 100,000,000 females Common amongst royalty in Europe Queen Victoria = Carrier Turner Syndrome Also called XO, because people with Turner’s have only 1 X chromosome No Y means Turner’s people are female. However, no ovaries develop, so they don’t undergo the body changes of puberty and they are sterile. Hormone treatment cures all but the sterility. Other symptoms: short stature, webbed skin and low hairline at the neck, some oddities of spatial perception. Not retarded. Klinefelter Syndrome Non-disjunction can also result in a person with 2 X’s and a Y: XXY. This is called Klinefelter Syndrome. The Y chromosome makes a person with Klinefelter’s male: possessing testes. Symptoms: female body hair pattern, breast development, sterile, can be some developmental delay or retardation, especially for verbal skills. Often not diagnosed, or diagnosed only accidentally. Most symptoms are helped by testosterone treatment. Other Number Variations Triplo-X, having 3 X chromosomes. No Y chromosome means female. Many with this syndrome are undiagnosed because they have no symptoms. Some have slight social and developmental problems, especially language-related. Occasional fertility problems, but many have normal fertility. Not well studied. XYY: having 2 Y chromosomes plus an X. Male because they have a Y. Many are never diagnosed due to a lack of symptoms. Tend to be taller, more physically active, slightly retarded, prone to acne. A few oddities It is possible to be XY and female. Two ways this can happen: 1. the SRY gene can be inactivated by a mutation. If SRY doesn’t work, testes don’t develop and the embryo develops as a normal female. 2. In a condition called “androgen insensitivity”, the person is XY with a functional SRY gene, but her cells lack the testosterone receptor protein, so the cells don’t ever get the message that the testosterone is sending. Testes develop in the abdominal cavity, and no ovaries, fallopian tubes, or uterus develop. At puberty, the internal testes secrete testosterone, which gets converted into estrogen and the body develops as a normal (but sterile) adult female. XY women show some “male-like” features that make them good models Taller than most women Chiseled Jaw: Good Muscle definition: Don’t have as much body fat Hermaphrodites ?!? Hermaphrodite: An individual that has all female reproductive parts, and all male reproductive parts No such thing in Humans Hermaphrodites In some cases, androgen insensitivity is only partial: the cells respond a little bit to testosterone produced by the testes. The embryo develops with ambiguous genitalia, neither completely male not completely female. Another condition, congenital adrenal dysplasia, causes the adrenal glands to produce an abnormally large amount of testosterone in a female embryo, This can also cause development of ambiguous genitalia. Another rare condition: a chimera occurs when two separate embryos fuse together. This can result in a person with some XX cells and some XY cells. This condition is extremely rare: more people say they have it than actually do. Twins 2% of births Monozygotic (Identical) 30% of twins A single zygote splits into two. This happens between 1 to 9 days after the zygote forms. The twins share the same genome Dizygotic (Fraternal) 70% of twins Two separate eggs are fertilized with two separate sperm. Two totally independent zygotes are created. The twins have different genomes Conjoined twins – very rare (1 in 200,000) Identical twins who fail to completely separate after the 13th day after fertilization This may be due to the fusion, or incomplete separation of zygotes May be two fully formed individuals connected at various locations, or rarely, parasitic twins, where one is much smaller and less formed, or even completely contained. Sex-Influenced Traits Some traits appear to be specific to one sex, but are not sex-linked: their genes are not on the X chromosome. It is sex-influenced. The best human example is male pattern baldness. Baldness is dominant in males: heterozygotes and homozygotes both become bald. In females, baldness is recessive: only homozygotes (which are relatively rare) become bald. Also, females tend to lose hair more evenly than men, giving a sparse hair pattern rather than completely baldness.