Human Genetics - Chapter 14_1_

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Human Genetics - Chapter 14_1_ Powered By Docstoc
					Population genetics & Evolution
 Genetic change on an individual level
  takes the form of mutations &
 Genetic change occurs in populations in
  the form of allele frequencies
 Changing allele frequencies define
  evolution – the basis of all biology

 Population = An interbreeding group of the
  same species in a given geographical area
 Gene pool = The collection of all alleles in
  the members of the population
 Population genetics = The study of the
  genetics of a population and how the
  alleles vary with time
 Gene Flow = Movement of alleles between
  populations when people migrate and mate
        Allele Frequencies
                    # of particular allele
 Allele frequency = Total # of alleles in
                      the population

Count both chromosomes of each individual
Allele frequencies affect the genotype
  - The frequency of the two homozygotes
  and the heterozygote in the population
    Phenotype Frequencies
   Frequency of a trait varies in different

 The small genetic changes due to
  changing allelic frequencies in populations
 Five factors can change genotypic
    1) Nonrandom mating
    2) Migration
    3) Genetic drift
    4) Mutation
    5) Natural selection

   Refers to the formation of new species

   Occurs when enough microevolutionary
    changes have occurred to prevent
    individuals from one population to
    successfully produce fertile offspring

    Hardy-Weinberg Equation
 Developed independently by an English
  mathematician and a German physician
 Used algebra to explain how allele
  frequencies predict genotypic and
  phenotypic frequencies in a population of
  diploid, sexually-reproducing species
 Disproved the assumption that dominant
  traits would become more common, while
  recessive traits would become rarer
     Hardy-Weinberg Equation
         p = allele frequency of one allele
         q = allele frequency of a second allele

  p+q=1              All of the allele frequencies
                     together equals 1

p2 + 2pq + q2 = 1     All of the genotype frequencies
                      together equals 1

p2 and q2         Frequencies for each homozygote
   2pq            Frequency for heterozygotes
    Source of the Hardy-Weinberg

Figure 14.3                        9
Solving a Problem

Solving a Problem

Allele and genotype frequencies do not change
  from one generation to the next
Thus, this gene is in Hardy-Weinberg equilibrium
     Applying the Hardy-Weinberg
    Used to determine carrier probability
    Autosomal recessive diseases
       – The homozygous recessive class is used
         to determine the frequency of alleles in a
       – Phenotype indicates genotype

Figure 14.3                                           13
    Calculating the Carrier Frequency
       of an Autosomal Recessive

Figure 14.3                             14
Calculating the Carrier Frequency
   of an Autosomal Recessive

Calculating the Carrier Frequency
   of an Autosomal Recessive
 What is the probability that two
  unrelated Caucasians will have an
  affected child?
 Probability that both are carriers =
  1/23 x 1/23 = 1/529
 Probability that their child has CF = ¼
 Therefore, probability = 1/529 x 1/4 =
     Calculating the Risk with
          X-linked Traits
For females, the standard Hardy-Weinberg
 equation applies
 p2 + 2pq + q2 = 1
However, in males the allele frequency is
 the phenotypic frequency
 p + q= 1
Calculating the Risk with
     X-linked Traits

Hardy-Weinberg Equilibrium
   Hardy-Weinberg equilibrium is rare for
    protein-encoding genes that affect the

   However, it does apply to portions of the
    genome that do not affect phenotype

   These include repeated DNA segments
    – Not subject to natural selection

            DNA Repeats
 Short repeated segments are distributed
  all over the genome
 The repeat numbers can be considered
  alleles and used to classify individuals
 Two types of repeats are important
    – Variable number of tandem repeats
    – Short tandem repeats (STRs)

DNA Repeats

            DNA Profiling
 A technique that detects differences in
  repeat copy number
 Calculates the probability that certain
  combinations can occur in two sources
  of DNA by chance
 DNA evidence is more often valuable in
  excluding a suspect
    – Should be considered along with other
     types of evidence
Comparing DNA Repeats

             DNA Profiling
   Developed in the 1980s by British
    geneticist Sir Alec Jeffreys
    – Also called DNA fingerprinting

   Identifies individuals
    – Used in forensics, agriculture, paternity
      testing, and historical investigations

   Differing number of copies of the same repeat
     migrate at different speeds on a gel

Figure 14.8

   Jeffreys used his
    technique to
    demonstrate that
    Dolly was truly a
    clone of the 6-year
    old ewe that
    donated her

    DNA Profiling Technique
1) A blood sample is collected from
2) White blood cells release DNA
3) Restriction enzymes cut DNA
4) Electrophoresis aligns fragments by size
5) Pattern of DNA fragments transferred to
   a nylon sheet
     DNA Profiling Technique

6) Exposed to radioactive probes
7) Probes bind to DNA
8) Sheet placed against X ray film
9) Pattern of bands constitutes DNA profile
10) Identify individuals

Box Figure 14.1   29
           DNA Sources
DNA can be obtained from any cell with a
STRs are used when DNA is scarce
If DNA is extremely damaged, mitochondrial
   DNA (mtDNA) is often used
For forensics, the FBI developed the
  Combined DNA Index System (CODIS)
  - Uses 13 STRs

The probability that any two individuals have same
  thirteen markers is 1 in 250 trillion
    Population Statistics Is Used to
        Interpret DNA Profiles
   The power of DNA profiling is greatly
    expanded by tracking repeats
    – # of repeat copies assigned probabilities
      based on observed frequency in a
   The product rule is then used to
    calculate probability of a certain repeat
   To Catch A Thief With A Sneeze

Table 14.6

Table 14.6

Using DNA Profiling to Identify
Recent examples of large-scale disasters
  - World Trade Center attack (2001)
  - Indian Ocean Tsunami (2004)
  - Hurricane Katrina (2005)
  - Reuniting Holocaust survivors

Challenges to DNA Profiling

         Genetic Privacy

Today’s population genetics presents a
  powerful way to identify individuals
Our genomes can vary in more ways than
  there are people in the world
DNA profiling introduces privacy issues
  - Example: DNA dragnets

Principle: Allele frequencies in a population will remain constant unless one or more
factors cause those frequencies to change. When allele frequencies remain
constant the alleles are said to be in Hardy-Weinberg Equilibrium.

In addition to allele frequencies remaining constant when a population is in H-W
equilibrium, genotype proportions also remain constant and can be calculated from
the allele frequencies.

If p is the frequency of allele A for a trait and q is the frequency of allele a for
the same trait, then genotype proportions are given by:

(p + q)2 = p2 (AA) + 2pq(Aa) + q2(aa)

p + q = 1
Where p= the frequency of the dominant allele and q= the frequency of the
recessive allele.

**All the alleles in a population will total 100% or in this case 1.

P2 + 2pq + q2 = 1

p = % homozygous dominant
2pq = % heterozygous
q = % homozygous recessive
This determines the genotype frequencies in a population at H-W equilibrium.
                                     Let’s Practice!!

1.)       If a population has a dominant allele found at a frequency of 90%, what are the
percentages of homozygous dominant, heterozygous, and homozygous recessive
individuals in the population?

ANSWER: The p = 0.9 so q = 0.1 because the total will be 100%, or 1.
Now use the formula to get the rest: p2 + 2pq +q2 = 1

Homozygous dominant: p2 = 0.8 or 81%
Heterozygous: 2(0.9)(0.1) = 0.18 or 18%
Homozygous recessive: q2 = 0.01 or 1%

Total 100%; note that the dominant allele does not eliminate the recessive allele…

2.)      If a gene (A) is in H-W equilibrium and the value of p is 0.3, what proportion of
the population has each genotype?


The proportion of AA individuals is p2 or 0.09
The proportion of Aa individuals is 2pq or 0.42
The proportion of aa individuals is q2 or 0.49
**All the genotype proportions MUST add up to 1!!
                                  Now It’s Your Turn…

1.)     You have sampled a population in which you know that the percentage of the
homozygous recessive genotype (aa) is 36%. Using that 36% calculate the following:

         •The frequency of the ‘aa’ genotype
         •The frequency of the ‘a’ allele
         •The frequency of the ‘A’ allele
         •The frequencies of the genotypes ‘AA’ and ‘Aa’
         •The frequencies of the two possible phenotypes if ‘A’ is completely dominant
         over ‘a’.

2.)       There are 100 students in a biology class. Ninety-six did well in the course, but
4 blew it totally and received a grade of F. In the highly unlikely event that this trait is
genetic rather than environmental, involves dominant and recessive alleles, and if the 4%
represents the frequency of the homozygous recessive condition, calculate the following:

         •The frequency of the recessive allele
         •The frequency of the dominant allele
         •The frequency of heterozygous individuals
         •The number of homozygous dominant individuals

3.) Within a population of butterflies, the color brown (B) is dominant over white (b).
Discovering that 40% of the butterflies are white, calculate the following:

         •The percentage of butterflies in the population that are heterozygous
         •The frequency of homozygous dominant butterflies

4.) Cystic fibrosis is a recessive condition that affects about 1 in 2,500 babies in the
Caucasian population of the U.S. Calculate the following:

         •The frequency of the recessive allele in the population
         •The frequency of the dominant allele in the population
         •The percentage of heterozygous individuals (carriers) in the population

5.) The ability to taste PTC is due to a single dominant allele, ‘T’. You samples 215
individuals at C.O.C, and determined that 150 could detect the bitter taste, and 65 could
not. Calculate the following:

         •The frequency of the recessive allele in the population
         •The frequency of the dominant allele in the population
         •The percentage of the heterozygous individuals (carriers) in the population
         •The number of heterozygous individuals in the population

          Conditions that Change
            Allele Frequencies
    Five conditions change allele frequencies
      (and ultimately phenotypic frequencies)
      1) Nonrandom mating
      2) Migration
      3) Genetic drift
      4) Mutation
      5) Selection
Figure 14.3                                     42
           Nonrandom Mating
   Nonrandom mating indicates that
    individuals of one genotype reproduce
    more often with each other
    – people marry ones similar to ourselves about
      80% of the time
   Traits that influence our mate choice
    – Physical appearance
    – Ethnic or religious preferences
    – Intelligence and shared interests
Alters Allele

Examples of Nonrandom Mating

    Males fathering many
     – Arnold (South Africa)
          Increase in frequency of a
                 dominant dental disorder in
                 the Cape population
     – Genghis Khan (Asia)
          16 million men living today share
           his Y chromosome

Examples of Nonrandom Mating
   Hopi Indians – Albinism

   Ashkenazi Jews – Tay-Sachs disease

   Consanguinity – Marriage between
    blood relatives

   Endogamy – Marriage within a
   Individuals migrate and move genes from one
    area to another
    – The addition or removal of alleles will alter the
      genotypic frequencies

   Genetic effects of migration are reflected in
    current populations

   Changes in allele frequency can be mapped
    across geographical or linguistic regions

Migration Alters Allele Frequencies

               Genetic Drift
   Genetic drift is the change in allele
    frequency when a small group separates
    from the larger whole

   Caused by random sampling errors

   Allele frequency changes are unpredictable

   More pronounced in small populations
Genetic Drift Alters Allele Frequencies

                Genetic Drift
   Events that create small populations
    enhance the effect of genetic drift
    –   Founder effect (founding a new population)
    –   Bottlenecks (natural disaster, famine)
    –   Geographic separation (islands)
    –   Cultural separation

              Founder Effect
   Occurs when a small group leaves home to
    found new settlements

   The new colony may have different allele
    frequencies than the original population
    – It may, by chance, either lack some alleles or
      have high frequency of others

    Examples of Founder Effect
   French Canadians of Quebec
    – Have only 4/500 alleles for BRCA1 gene

   Dunker community of Germantown, Penn.
    – Descendants of German immigrants who came
      between 1719 and 1729
    – Have different distribution of blood types than
      the German native and non-Dunker neighbor
Table 15.2
 Genetic Drift and Nonrandom
Small population size increases the probability of
Increases recessive phenotypes in population

  - Amish and Mennonite populations of Penn.
  marry predominantly within their religious groups
  - Maintain their original small genetic pool
  - Increased incidence of otherwise rare traits
        Ellis-van Creveld syndrome
Figure 15.6                          57
           Population Bottlenecks
   Occurs when a large population is
    drastically reduced in size

    – Rebounds in population size occur with
      descendants of limited number of survivors

          Therefore, new population has a much more
           restricted gene pool than the large ancestral

Population Bottlenecks

Examples of Population Bottlenecks
   Pingelapese people of Micronesia
    – Bottleneck created by a typhoon
   Cheetahs in S. and E. Africa
    – Bottleneck created by changing habitats (after
      the most recent ice age) and mass slaughter
      by humans in the 19th century
   Ashkenazi Jews
    – Massacres and nonrandom mating between
      survivors contributed to high incidence of
      certain disorders
Examples of Population Bottlenecks

   Mutations are a major and continual
    source of genetic variation in populations
    – Can introduce new alleles
    – Can convert one allele to another

   Mutation has a minor impact (most are
    silent) unless coupled with another effect
    such as small population size or selection

Mutations Alter Allele Frequencies

   Selection eliminates deleterious alleles

   However, harmful recessive alleles are
    maintained in heterozygotes and are
    reintroduced by mutations

   Genetic load is the collection of recessive
    deleterious alleles present in a population

            Natural Selection
   Is the differential survival and reproduction
    of individuals with a particular

 Negative selection = Banishment of a
  dangerous trait
 Positive selection = Retaining an
  advantageous trait
 Both lead to changes in allele frequencies

Natural Selection Alters Allele Frequencies

           Artificial Selection
   Controlled breeding with the intent of
    perpetuating individuals with a particular

   Examples:
    – Crop plants
    – Pets

Natural Selection and Tuberculosis
   TB infections have historically swept across
    susceptible populations killing many

   Natural selection operating on both the bacterial
    and human population has lessened the
    virulence of the infection

   Recent resurgence reflects AIDS and increasing
    bacterial resistance to antibiotics

 Bacterial Antibiotic-Resistance
 Bacteria become resistant in two ways:
     1) Mutation passed from one bacterial
  generation to another by cell division
     2) Groups of resistant genes are passed on
  transposons; they are transmitted from cell to
  cell by plasmids

   A particularly dangerous strain is methicillin-
    resistant Staphylococcus aureus (MRSA)

    Natural Selection in HIV
 RNA or DNA viruses replicate often and
  errors are not repaired
 Viral mutations accumulate rapidly
 In HIV infection, natural selection controls
  the diversity of HIV variants within the
  human body as the disease progresses
 The human immune system and drugs to
  slow infection become selective agents
 Combinations of drugs that act in different
  ways are more effective
   Initially the immune system identifies and
    eliminates many cells infected with HIV
   Mutations occur in the virus
   Viral mutations allowing increased replication or
    immune system evasion are favored
   Gradually the immune system of the infected
    person can no longer fight off the HIV infection
   HIV infection progresses to AIDS when lack of an
    intact immune system leads to opportunistic
   Now becoming chronic rather than lethal

      Balanced Polymorphism
   Persistence of harmful recessive alleles
    due to heterozygotes

   When two or more forces (environmental
    threat vs. harmful allele) act in different
    directions on alleles of a gene

 Also called heterozygote advantage
    - Have a reproductive advantage
  under certain conditions
Balanced Polymorphism

Sickle Cell Disease and Malaria
   The beta hemoglobin gene exhibits balanced

   Sickle cell allele causes the recessive sickle cell
    anemia trait (when homozygous) and is
    therefore under negative selection

   Sickle cell allele helps protect heterozygotes
    from malaria therefore under positive selection

Sickle Cell Disease and Malaria

Figure 15.12                      77
Prion Disease and Cannibalism

   Kuru is an illness causing brain
    degeneration in the Foré people in New

   The tribe practiced ritual cannibalism

   Heterozygotes for a protein folding gene
    may protect from transmissible spongiform
Cystic Fibrosis and Diarrheal
 Diarrheal diseases can be major killers
 CFTR protein affects chloride channels
 Cholera toxin causes chloride channels
  to open producing severe dehydration
 Typhoid fever requires a functional
  CFTR for bacteria to enter the cell
 Heterozygotes have some protection
  from these two bacterial diseases
      Phenylketonuria (PKU)

 The diversity of PKU mutations suggests
  that the disease has arisen more than once
 In most populations, point mutations in the
  PAH gene cause PKU
 However, all Yemeni Jews in Israel with
  PKU have a large deletion
 Records indicate that the deletion arose in
  San’a (the capital of Yemen)
    - It then spread among Yemenite Jews
Phenylketonuria (PKU)

 The word eugenics was coined in 1883 by Sir
  Francis Galton to mean “good in birth”
 On a societal level, eugenics is the control of
  human reproduction with the intent of changing
  a population’s genetic structure
 Positive eugenics = Promotes reproduction
  among those considered superior
 Negative eugenics = Interferes with
  reproduction of those judged inferior

 Eugenics extends the concept of natural
  selection and Mendel’s laws but does not
  translate well into practice
 Some people consider modern genetic
  screening practices eugenic
    - However, genetic testing typically
  aims to prevent or alleviate human
 Wars may have eugenic consequences


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