Science of HEREDITY                                                               Key Concepts*
studies how the form [morphology]
               and appearance  [phenotype]  of an organism

are established by its genes as influenced by the environment.
  essence of heredity... 
from the millions of different species, each reproduces itself, faithfully,
       yielding progeny that belong to the SAME species, i.e., the parent organism hands
       down information specifying, in exacting detail, the characteristics of its offspring;
       this phenomena of Heredity is central to the definition of Life...
       ability of a cell to faithfully copy its DNA instructions into identical progeny cells.
  a genetic pedigree





  Two aspects to heredity...

  Mendelian Genetics - 
Quantitative analysis of inheritance of morphological characters in organisms....
                experiments which established the basic principles & laws
                that predict the pattern of inheritance from generation to generation
a genetic pedigree*

  Molecular Genetics - 
     physical properties of molecules (DNA & RNA)
                               as they effect patterns of inheritance

                      Central  Dogma  of  Molecular  Biology 
DNA --> transcription --> RNA -- translation --> Protein





MENDELIAN   GENETICS...                Mendel Museum

Gregor Mendel was an Augustinian monk (later abbot) at the Abbey of St. Thomas
                in Brno (today part of the Czech Republic)           

   bred sweet pea  flowers*   to produce progeny via  self pollination*  &  cross pollination*
                Mendel made crosses between true breeding parents 
                for a single genetic character (morphological trait)
                with 2 different phenotypes (appearances)
   Mendel's 7 true breeding traits in pea plant genetic crosses
* Concept Activity 14.2- Gregor's Garden

           generation                     experimental genetic cross
        Parental       round seed     x    wrinkled seed
            F1            round seed                 
[ x themselves]
            F2           3 round
* seed  to  1 wrinkled* seed   
                                        Concept Activity - 14.1 - Mendel's Experiments : Monohybrid Cross
 another example using flower color in peas*




Particulate Inheritance

   Physical inheritance is discernible as   "particles"   or   "factors",  which are
       -  discrete entities w own integrity                 (no blending of traits)
       -  trait is preserved through inheritance 
      (over generations)
       -  occur within the individual in PAIRS             (

       -  some particles mask expression of others  (round masks wrinkled)

 Law of Mendelian Segregation...    
when gametes are formed 
               -  2 particles of inheritance in an individual segregate from each other
               -  each gamete receives 1 particle from each parent







  Modern Interpretation of Mendel's Hypothesis...
        - particles are GENES...  entities definable in molecular terms [DNA segment]
        - referred to by alphabetic taxonomy =   A & a,   B & b,   C & c,   etc...
        - trait may occur in different morphological forms...  called ALLELES
               allele - a gene which codes for different forms  
(round,  wrinkled,  square)
                                           of a similar protein, that governs that phenotype
occur on chromosomes at a specific  GENE LOCUS* -
        - some traits mask expression of others - dominant  &  recessive allele traits
                      recessive -  trait that disappears in the F1 generation
                      dominant  -  trait that does not disappear in the F1
        - each individual possess 2 alleles for a specific trait, thus
                                                         RR  -   homozygous dominant
                                                         Rr   -   heterozygous
                                                         rr   -   homozygous recessive




Mendelian Monohybrid Genetic Cross










gametes (4)










 Punnett Square



 Results of Monohybrid Cross              
PHENOTYPE (APPEARANCE)           3 round    to   1 wrinkled           ratios*
(ALLELE MAKEUP)      1  (RR)  to  2 (Rr)  to  1 (rr)     numbers*

Mendel's hypothesis is scientifically testable 
- his premise [a testable hypothesis] predicts that F1  is a heterozygote [Aa]
 - testable experiment - do a Testcross/Backcross*
                                                  cross of unknown genotype to homozygous recessive

predict 1:1 ratio r r

          if  heterozygote

R Rr Rr
r rr rr
predict all the same r r
          if  homozygote R RR RR

R Rr Rr


genotype RR Rr rr


round round wrinkled
starch content high median  low
starch grains numerous median few
reducing sugar low median high
high median low

starch  +  G1P -->  starch (n+1)


                thus : dominant allele R of the seed shape gene codes for the enzyme 
                                                        UDP-glucose (glycogen) phosphorylase 
                           which makes starch,  which is hygroscopic and absorbs water, 
              making the seed appear round in the dry seed state.







 Molecular Basis of some of Mendel's Traits...

    in 1990 - the gene for wrinkled seed was determined to be due to
                            the starch branching enzyme UDP-glucose (glycogen) phosphorylase

                    the recessive was caused by a  transposon-like  insertion      
                    into the starch branching enzyme's coding region   

    in 1997 - in the pea plant (& in the plant Arabidopsis) gene called   Le
                            which controls stem length (mutants are shorter) was identified

                                 the gene codes for the enzyme: GA3b-hydroxylase, which converts
                            two precursors of Gibberellic Acid into active GA3b,
                            GA3b is a plant hormone that promotes stem growth & fruit set.






Incomplete Dominance -  figure*   vs.   Blended Inheritance    
                 can it still be explained by Mendel's Law's?
                 - yes. neither gene is dominant,   i.e., both contribute to expression of the trait

   Mendel's Law of Independent Assortment
       a dihybrid cross demonstrates Independent Assortment
          dihybrid cross involves 2 characters or traits -
               new combinations of traits, not exhibited by either parent, are seen
                                        parentals     -  progeny look like parents
                                 non-parentals     -  progeny don't look like either parent


                                             DOMINANT            RECESSIVE
                flower color                W = red                w = white
                seed color                    G = green             g = yellow 

P1         WWGG         x        wwgg                         true breeding
                F1          WwGg         (x   WwGg self cross)       what's the phenotype?





 F2      phenotypes  
flower color    seed color           ratio

parental  red          green      9 of 16
     non-parental white      green      3 of 16         9:3:3:1
     non-parental     red yellow     3 of 16
parental  white       yellow     1 of 16

       Each trait alone    red (3)     = 12 of 16      white (1)     = 4 of 16
                  3:1               green (3)   = 12 of 16     yellow (1)     = 4 of 16

                traits - are distributed to progeny independent of each other
                          - thus, genes must occur on different chromosomes 
                                                    Sumanas, inc. animation - independent assortment
                a dihybrid cross*    (another look)         (a model dihybrid cross*)
                                                                          Student CD Activity - 10.1 Inheritance of Two Traits


Chromosomal Theory of Inheritance*
     Walter Sutton & Theodor Boveri    (1902-1903)
          looked at spematogenesis and oogenesis, especially in grasshopper & sea urchins  
          described chromosomes & observed MEIOSIS & suggested...
                   -  hereditary traits are carried in sperm & egg cells
                   -  on chromosomes
                   -  chromosomes obey Mendel's laws

                       >  chromosomes occur in pairs, as do "particles"     (homologs)
                       >  chromosomes segregate at meiosis, as do "particles"
                                 via Mendel's Law of Segregation      (homologs/chromatids separate)
                       >  chromosomes sort independently  of each other
                                 via Mendel's Law of Independent Assortment  - fig 15.2 (laws)*





 Golden Age of Genetics:     CHROMOSOMAL LINKAGE
Thomas Hunt Morgan ... Univ. of Columbia geneticist - fruit fly*     [calvin bridges]
        sex determination & genes & their traits are linked to specific loci on chromosomes 

  2 types of CHROMOSOMES -
1. AUTOSOMES - the non-sex chromosomes (everything else:  44 + 2)
* - photographic map of a species chromosomes

       2. SEX chromosomes (X and Y) - show a different structural morphology   pic*
sex determination* -->  heterogametic sex (xy)  &  homogametic sex (xx)                                                Y-chromosome - determines maleness & holds Short Tandem Repeats 

    SEX LINKED Recessives*    when a trait's gene is carried only on an X chromosome.
      Xa Xa   vs.   Xa Y     No Y trait thus...    HEMIZYGOUS (males)      figure* 
                                             ex: red green colorblindness (males = 8% and females 1%)
                                                   others:  hemophilia,  albanism,  myopia,  Duchenes' M.D.
                Sample Genetics Problems*             end material for test #2






Autosomal Linkage
...  (crossing over & maps)
       -  two traits are carried on a single chromosome   ___R__y__
       -  do not sort independently
   -  crossing over will allow us to map position of genes
                       mapping - frequency of cross over exchange is proportional
                                        to relative distance between 2 genes.

generation genotype phenotype
parental RRYY x rryy round/yellow wrinkled/green


Testcross RYry   x  ryry round/yellow wrinkled/green

if linked

           if not linked
  ry         ry 
RY RYry RY RYry    (RrYy) 
ry ryry  Ry  Ryry    (Rryy)
rY rYry     (rrYy)
ry  ryry     (rryy)

          1 : 1

         1 : 1 : 1 : 1


            we do an actual F1 testcross of linked genes; predicts 50:50 progeny.   
    BUT;    get following results...    NOT  1 :[RYry & ryry],  but rather we get...
  round & yellow         41.5%     R_Y_    parental phenotype
                       wrinkled & green     41.5%     rryy      parental phenotype
                       round & green           8.5%     R_yy     non-parental phenotype
                       wrinkled & yellow      8.5%     rrY_     non-parental phenotype 
                                                                                         (17% non parentals)



HOW COME ???    because of   CROSSING OVER...
            or homologous recombination... the process by which two
             non-sister chromatids, paired up during prophase 1 of meiosis,
             exchange equal distal portion of their chromosomal DNA

         A             B                                     C

          a              b                                     c








Frequency of crossover exchange...
exchange of chromatids pieces of a homologous pair during synapsis at a chiasma... 
   is GREATER the FARTHER apart 2 genes are

is proportional to relative distance
between 2 linked genes

   Relative distance is measured as...
   1% crossover frequency =
1 map unit of map distance
              above CO Freq  =   8.5% + 8.5% = 17%

    1%   CrossOver  Freq   =    1   centiMorgan






Let's determine the map for the genes   R  [shape]   &   Y  [color] 


   1.   Genes R & Y revealed 17% CO frequency of exchange (above)
          thus genes  R  and  Y  are 17 map units (centiMorgans) apart
   2.  now,  genes  R  and  X  reveal 5% crossover frequency ???
   3.  thus, genes  Y and  X  could reveal either a 12% or 22%  CO frequency???

      X   5cm  .    5cm    X                              RRXX  x  rrxx  -->  RXr -> testcross
                R                   17cm            Y            but 5% are R_xx & rrX_

                 R   5cm     X      12cm            Y 

        5cm   R                    17cm           Y      YYXX yyxx --> YXyx    =  % ?
                            genes are linear & occur at specific loci
a mapping example*







Gene Interactions...  and    Mendelian ratio anomalies
Complementary Genes - 2 genes are mutually dependent to show phenotype
        Purple flower color   requires a color protein  &  a protein complement
            P         PPCC x ppcc                                 both required for phenotype                          
            F1             PpCc

            F2      9    P_C_      purple
                      3    ppC_      white            a  9 : 7  ratio
                      3    P_cc      white                                   not 9:3:3:1  
                      1     ppcc      white
*  - works in similar fashion: often involves B = melanin gene; 
        where a gene at one locus modifies the phenotype (C = deposits pigment) of gene
        at a second locus (Black or brown) and results in an altered dihybrid ratio.
                9 B_C_               3 bbC_                  3 B_cc     1 bbcc          9:3:7
                   black                  brown                           white




Polygenic [Quantitative Trait] Inheritance
        2 or more genes affect 1 phenotype
           usually with quantitative characters,
with a continuous scale of measurement...
- height,  weight,  color
* (and a  polygenic*model), etc...

     1 gene influences many phenotypic traits...
                    - a mutant defect in collagen gene = multiple morphological deformities...
                              as the
main component of cartilage, ligaments, tendons, bone and teeth.

                    - sickle cell gene results in many physiological disorders due to key
                                            metabolic role that gene plays in physiology of blood












Classical Human Genetics  

   Pedigree Analysis*

   Pedigree Symbols


 Pedigree drawing software

Some Examples of Human Genetic Traits...
    - Widow's peak&   free ear lobes*,   +   finger hair   &   freckles,   
    -  Blood Groups
* - 4 phenotypes O, A, B, and AB  
                                                        due to RBC surface carbohydrates
    - Sex linkage - trait carried on X-chromosome 
                              red-green colorblindness, hemophilia
*    [ genealogy ]
    - Mistakes of Meiosis -  abnormal chromosome structure
                             Downs Syndrome
* - Trisomy 21 - due to chromosome non-disjunction
                             & examples via non-disjunction in sex chromosomes
    - Inborn Errors of Metabolism - defective enzymes due to recessive mutations





Inborn Errors of Metabolism - non-functional enzymes          [genes & diseases]

        PHENYLKETONURIA - [PKU]     pp                   1/10,000 births
            disfunctional phenylalanine hydroxylase on chromosome 12
               PHE  --x-->   tyrosine    --> -->   degraded & excreted
                   accumulates - blood/brain barrier = mental retardation
        ALKAPTONURIA         aa       A. Garrod in 1908     
            homogentisic acid oxidase --x--> ALKAPTON
*  [urine oxidizes black & ochronosis]
                    1st suggestion that effect of genes was to make proteins
                    and disease is due to a defective enzyme/protein.
        TAY SACHS                tt                      
            1/300,000 births 
            defective (hexosaminidase-A) enzyme = high ganglioside fats in nerves --> death
            Ashkenazic Jewish ancestry show  
1/ 3,600 births   &    1 / 30  is  Tt
        SICKLE CELL  s            ss      
                      1/6,000 births
                        defective beta polypeptide of Hb
                        improper folding of Hb --> clogs capillaries
[umbilical cord blood stem cell transplant of Keone Penn  update]







  How many recessive alleles are there in a given population?

      It is easy to determine how many recessives there are in a population -
            Just Count them, but...              
[phenotype = aa & shows strait]

      but, How do we know how many Heterozygous Carriers there are in a population?


              We can determine the number of carriers for a recessive gene by using...

                                                         Hardy-Weinberg Equilibrium*









Chromosomal Abberations  -  Mistakes of Meiosis
   Aneuploidy - Variation in chromosome #    monosomy - 1 less than normal
                                                                        disomy - normal (diploid)
                                                                        trisomy - 1 more than normal 
       via   non-disjunction
*    (trisomy 21 - Down Syndrome - frequency vs. age*]
Aneuploidy of SEX chromosomes in the gametes: (non-disjunction of XX)

X X 




  X0     X     or    Y Y0       XXX    X   or   Y   XXY


   Turner syndrome
   1/5000 births
90% abort -
   appears female
   often sterile TSS

                               dies      triple X syndrome
                                             1/1000 births
                                             no visible symptoms
                                             may be sterile
                                           some developmental issues

   1/2000 births
    appears male












Chromosomal Abberations due to alterations of Chromosome Structure

      alterations of chromosomes can lead to 4 types of structural changes
c7 figure 15.15*

               1) deletions - chromosome fragment without centromere is lost
                       cri du chat: deletion on chromosome 5
                                          mental retardation, small head & face, cry of a cat, fatal
               2) duplications - a segment is repeated
               3) inversions - a segment reverses is linear sequence
               4) translocations - both segments moves from one chromosome to another
                             reciprocal :  non-homologous chromosomes exchange pieces
                                                      chronic myleogenous lukemia - cancer of WBC
                                                      large portion of chromosome 22 with small tip of 9
              c7 fig 15.17
               non-reciprocal :  one chromosome transfers a segment without exchange
                                                    Downs's syndrome (5% of cases) small piece of 21 to 14







          the study of human improvement by genetic means, 
          historically... often suggested to be done by elimination of "inferior" genes. 

           aneuploidy, criminal inheritance, and eugenics????
               XYY syndrome  
karyotype    (of 197 violent criminals in a Scottish prison -
                                                           7 were XYY, statistically astronomical....
                                                           thus myth of criminal violence & XYY's)
               Richard Speck claimed to be an XYY "supermale" to get leniency by courts

   Amniocentesis -  fetal diagnosis
* - biochemical and cytological analysis of the
                                                             amniotic fluid surrounding a fetus.

   Sample Genetics Problems*


   Molecular Genetics*














 F1 parents of a F1 testcross  :  RYry  x  ryry 
                        linked same chromosome                   not  linked different chromosomes
                 ____R__Y___                    ____R____     ____Y___              
                 ____r__y___                     ____r____      ____y___               

F1 gametes  2 kinds gametes

4 kinds gametes recessive gametes*
____R__Y___ ___R___
____R__Y___ ___R___
____r__y___ ___r___
____r__y___ ___r___

                * the recessive parent: makes no difference whether genes are linked or not
back                     ____r__y___               or       ___r___  &  ___y___       










  AB Ab aB ab
Ab AABb AAbb AaBb Aabb
aB AaBB AaBb aaBB aaBb
ab AaBb Aabb aaBb aabb










a  Mendelian  anomaly ?


 [BARR Body*]




   Genomic Imprinting...
The phenotype expressed can open depend upon whether
         the allele (autosomal) comes from the 
 or   parent.
                    - often occurs during gamete formation
                    - either
  gamete or gamete is silenced
                    - zygote expresses only 1 of the 2 alleles & it is passed to all progeny cells
                    - within a given species imprinted genes are always either maternal or paternal


            ex:  1)  gene for insulin-like growth factor (Igf2)
                               - only the paternal allele is expressed  
C7e - fig 15.17a
                               - ratio anomalies occur when mutant allele is passed
C7e - fig 15.17b
                  2)  most other imprinted genes are involved in embryonic development,
                           where presence of only one allele of some genes is tolerated


           cause:  seems likely to be methylation of CYS nucleotides of the affected allele
                         that results in heterochromatinization (inactivation)