Disorders & Sex Linked Traits

Honors BiologyUnit 52012-2013Genetic Disorders&Sex Linked TraitsRecessive DisordersDisorders that are only expressed in the phenotype when 2 recessive alleles are present.

DD = NormalDd = Carrierdd = Affected by disorder

2 Examples of Recessive DisordersTay-Sachs DiseaseA 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 JewsThis 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% Normal50% Carriers25% Tay-SachsCystic FibrosisThick mucus is produced by the bodyMucus 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% Normal50% Carriers25% Cystic Fibrosis

Dominant DisordersDisorders that are expressed in the phenotype of heterozygous and homozygous dominant individuals

DD = AffectedDd = Affecteddd = Normal

2 Examples1) Huntingtons DiseaseBrain cells degenerate over time

Mood swings, loss of muscle control, loss of memory and inability to learn, death. Usually adult-onset, appears around ages 40-50Outlook is 10-15 years of survivablity

hh = NormalHH or Hh = will get and die of this diseasePerson with Huntingtons and a person without Huntingtons

Hh x hh Offspring: 50% Huntingtons50% NormalHuntingtons is most common in certain parts of Venezuela (700 in 100,000)

Generally affect 3-7 in 100,000 of European ancestryLess common in African-American & Asian American

2) Marfans SyndromeDefective gene for fibrillin-1 that results in abnormal connective tissue

Aorta may stretch or become weak, causing aortic rupture, the leading cause of deathEye/lens problemsExcessive long bone growth (long arms & fingers)Hypermobile joints (too flexible)

Chromosome Structure VariationsChromosomes 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 VariationsThe 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 VariationsChanges 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 VariationsIn 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:AneuploidyExcept for the X and Y, humans dont 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. *Having 3 chromosomes of each kind instead of 2

*Normally trisomy results in death.Trisomy:1 ExampleDown 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 Downs 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 Downs. Occurs about 1 in 1000 births.

Sex Linked TraitsSex Linked TraitsTraits that occur on the X or Y chromosome

X-linked traits are traits found on the X Chromosome

Sex-linked GenesGenes 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 GenesIn 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 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 fathers 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 blackX = orange X1 = black

Males: XY = orange / X1Y = blackFemales: XX = orange / X1X1 = black / XX1 = calico

Because individual cells determine which X chromosome to deactivate, the patches of color arise

ColorblindnessWe 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).

ColorblindnessMost 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 dotsThe dot pattern makes up a numberWhat number do you see?

With Color Vision:

This one you can even see in black and whiteColor 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 #: 5What do the colorblind see?NORMALPROTAN:Red BlindDEUTERAN:Green BlindTRITAN:Blue BlindREDYELLOWGREENCYANBLUEMAGENTATypes of Colorblindness

Types of Colorblindness NormalNo color visionProtanopia: no redDeuteranopia: no greenTritanopia: no blueHow to write Alleles for X-Linked TraitsWomen:Normal: XBXBCarrier: XBXbColorblind: XbXb Men: Normal: XBYColorblind: XbY

HemophiliaHemophilia 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 1980s, 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 males1 in 100,000,000 females

Common amongst royalty in Europe

Queen Victoria = Carrier

Turner SyndromeAlso called XO, because people with Turners have only 1 X chromosomeNo Y means Turners people are female. However, no ovaries develop, so they dont 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 SyndromeNon-disjunction can also result in a person with 2 Xs and a Y: XXY. This is called Klinefelter Syndrome.The Y chromosome makes a person with Klinefelters 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 VariationsTriplo-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 odditiesIt is possible to be XY and female. Two ways this can happen:

1. the SRY gene can be inactivated by a mutation. If SRY doesnt work, testes dont 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 dont 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 modelsTaller than most womenChiseled Jaw:Good Muscle definition:Dont have as much body fat

Hermaphrodites ?!?Hermaphrodite: An individual that has all female reproductive parts, and all male reproductive parts

No such thing in HumansHermaphrodites 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.

Twins2% of birthsMonozygotic (Identical) 30% of twinsA 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 twinsTwo 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 fertilizationThis may be due to the fusion, or incomplete separation of zygotesMay 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 TraitsSome 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.