Human Genetics

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Human Genetics
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Introduction

• Genetics is no longer just taking Punnett squares
  and doing a cross to learn.
• The field has become molecular like most biology.
• We are studying it on the gene and chromosomal
  level and learning vast amounts about how our
  genes have control of out lives by making the
  proteins the govern many actions in the human
  body and that also serve a building blocks in
  many structures.
• We are also wanting to find out how much of what
  we are is genetics and how much is or at least
  influenced by the environment. Ex) Personality
  ?????

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Pedigree Analysis

• This is just like tracing a family tree only a
  molecular tree based on the chromosomes that have
  been passed to you and your family genetically.
• Ex) Skin color, blood type, many phenotypic
  characteristics can be tracked and mapped.
• This mapping allows us to make accurate
  predictions on the outcome of any one couples
  children with in a marriage by knowing if they
  express or carry gene for certain phenotypic
  traits or genetic disorders.
• They are used to try and figure out the genotype
  of individuals for a particular trait like,
  widows peak.
• So use phenotype to determine genotype

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Pedigree

• third generation lacks a widows peak, but both
  her parents have widows peaks, then her parents
  must be heterozygous for that gene

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• Dimpled chins
• Free ear lobe Attached ear lobe

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• Widows peak
• Bent little fingers
• Not bent little fingers

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• Non-hitchhikers thumb Hitchhikers thumb

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• Non pigmented iris
• Pigmented iris

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Cont

• When you know the genotype you can use
  probability to determine the outcome of a
  marriage or chances of outcomes. Ex) WwFf marries
  WwFf what chance is their of Wwff child?
• Inheritance of genetic disorders is the medical
  focus for using pedigree analysis
• Many disorders follow the simple rules of
  Mendelian genetic inheritance, but some do not.

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Human Genetic Disorders

• Many disorders are inherited by recessive traits.
  They range from non-life threatening like
  albinism to life threatening like cystic
  fibrosis.
• the allele codes for either a malfunctioning
  protein or no protein at all.
• Heterozygotes have a normal phenotype because one
  normal allele produces enough of the required
  protein
• The recessive disorder show up only in homozygous
  recessive individuals, Homozygous dominant do not
  have the allele at all, while all heterozygous
  individuals are carriers that do not show or
  express the disorder but can pass it on to
  another generation.

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Cystic Fibrosis (Recessive)

• strikes 1/2,500 whites of European descent and
  1/25 are carriers
• normal allele codes for a membrane protein that
  transports Cl- between cells and the environment
• If channels are defective or absent, there are
  unusually high extracellular levels of chloride
  that causes the mucus coats of certain cells to
  become thicker and stickier than normal.
• mucus build-up in the pancreas, lungs, digestive
  tract, and elsewhere favors bacterial infections
  if untreated children will die by age 5 and if
  treated can live past their 20s

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Sickle-cell diseaseRecessive (Codominant)

• affects one of 400 African Americans
• caused by the substitution of a single amino acid
  in hemoglobin.
• When oxygen levels in the blood of an affected
  individual are low, sickle-cell hemoglobin
  crystallizes into long rods causing the cells to
  deform into the characteristic sickle shape.
• This causes many problems so it is pleiotropic

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Cont

• If you are a carrier of sickle cell you still
  make some of the malformed hemoglobin protein.
  This is due to its codominance at a molecular
  level. Even though you may show no
  characteristics of the disorder at an organismal
  level.
• Many heterozygotes have the sickle cell trait
  which is strange for an allele with extreme
  effects in homozygous individuals for the allele.
  Why would so many still carry and slightly
  express a deleterious allele???
• Answer Evolution individuals with one
  sickle-cell allele have increased resistance to
  malaria, a parasite that spends part of its life
  cycle in red blood cells. Homozygous normal
  individuals die of malaria, homozygous recessive
  individuals die of sickle-cell disease, and
  carriers are relatively free of both

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Lethal Dominant Alleles

• Dominants alleles can cause problems also, they
  are just not as common as recessive problems. If
  a lethal dominant kills an offspring before it
  can mature and reproduce, the allele will not be
  passed on to future generations.
• What if the lethal dominant could hide or not
  rear its ugly head until late in life, It can
  Huntingtons Disease.
• Degenerative diseases of the nervous system that
  has no phenotypic effect until 35-45 years of age
• irreversible and as you might expect fatal.

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Cont..

• child born to a parent who has the allele for
  Huntingtons disease has a 50 chance of
  inheriting the disease and the disorder.

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Multifactorial Disorders

• It is not all cut and dry, many disorders are
  controlled by more the one gene or have multiple
  alleles or have some strong environmental
  control.
• Multi-factorial disorders include heart
  disease,diabetes, cancer, alcoholism, and certain
  mental illnesses, such a schizophrenia and
  manic-depressive disorder.
• We do not yet fully understand the role of genes
  on disorders like alcoholism that require a
  strong environmental effect.

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Chromosomal Inheritance

• It was not until 1900 that we began to understand
  that the heritable factors Mendel had talked of
  were chromosomes, it took another 50 years to
  learn the nature of what they were made of DNA
• Each chromosomes contains 100s to 1000s of
  genes and genes located on the same chromosome,
  linked genes tend to inherit together.
• With genetic recombination due to things like
  crossing over during mitosis and independent
  assortment we get new combinations and not just ½
  copies of mom and dad

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Alterations in Chromosomes

• gene mutations are not the only kind of changes
  to the genome that can affect phenotype. Changes
  in chromosomes can also have deleterious effects.
  
• Nondisjunction occurs when problems with the
  meiotic spindle cause errors in daughter cells
• They do not separate as they should
• sister chromatids may fail to separate during
  meiosis II.
• consequence of nondisjunction, some gametes
  receive two of the same type of chromosome and
  another gamete receives no copy.

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Chromosome Problems

• abnormal chromosome number or aneuploidy
• There are trisomy individuals who have 3 copies
  of 1 gene or 1 extra chromosome, 47. And monosomy
  who are missing 1 chromosome 45
• Ex. Trisomy of chromosome 21 causes down
  syndrome.
• Polyploidy, individuals have an entire extra set
  of chromsomes, this does not see to have as bad
  an affect as just having 1 extra instead of the
  whole set these individuals are usually normal or
  close to normal phenotypically.

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Breaking Chromosome Structure

• 4 types of breaks occur deletions, duplications,
  inversions, and translocations.
• Deletions and duplications are common in meiosis
• Duplications and translocations are typically
  harmful
• translocation or inversion can alter phenotype
  because a genes expression is influenced by its
  location.
• The number of problems these 4 can cause is
  almost limitless depending on where they occur.
• If they occur early in development and they are
  going to cause a deleterious effect then a
  miscarriage is usually the result.

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Chromosome Disorders

• Many alterations in chromosome or structure are
  not seen since the embryo with the alteration
  will be spontaneously aborted.
• But some do survive
• Down syndrome (Trisomy 21) results from
  non-disjunction and is 3 copies of chromosome 21
• affects one in 700 children born in the United
  States
• 21 is the smallest human chromosome but an
  extra copy severely alter the phenotype of an
  individual
• Frequency of the occurrence goes up with age of
  the mother.
• in 1500 births if the mother is younger then 30.
  If the mother is over 45 there is a 1 in 46
  chance.

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Sex Chromosomes

• Problems in the sex chromosomes are usually not
  lethal but can have dramatic effects on
  individuals.
• because the Y chromosome contains relatively few
  genes.
• extra copies of the X chromosome become
  inactivated as Barr bodies in somatic cells so
  the effects do not show up
• Klinefelters syndrome, an XXY male, occurs once
  in every 2000 live births.
• These individuals have male sex organs, but are
  sterile.
• There may be feminine characteristics, but their
  intelligence is normal.

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Cont.

• XYY tend to somewhat taller than average.
• XXX females are normal and occur 1/2000 births
• X ,Turners syndrome, females produce immature
  females

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References

• Jack Brown M.S. Biology
• Starr and Taggart The Unity and Diversity of
  Life 10th edition 2004 Thomson Brookes/Cole
• Campbell and Reece Biology 6th edition. Pg 1-23
  2002 Benjamin Cummings.
• Microsoft Encarta Encyclopedia 2004
• Raven and Johnson Holt Biology 2004 Holt,
  Rinehart and Winston.