Beyond Mendel’s Laws of Inheritance

Extending Mendelian genetics  Mendel worked with a simple system  peas are genetically simple  most traits are controlled by a single gene  each gene has only 2 alleles, 1 of which is completely dominant to the other  The relationship between genotype & phenotype is rarely that simple

Incomplete dominance  Heterozygote shows an intermediate, blended phenotype  example:  R= red allele and R w = white allele  RR = red flowers  R w R w = white flowers  RR w = pink flowers  make 50% less color RRWWRW

Incomplete dominance true-breeding red flowers (RR) true-breeding white flowers (R w R w ) X P 100% 100% pink flowers F 1 generation (hybrids) self-pollinate 25% white F 2 generation 25% red 1:2:1 50% pink Phenotypic and genotypic ratios the same (RR w )

Codominant alleles will both be completely expressed. –Codominant alleles are neither dominant nor recessive. –The ABO blood types result from codominant alleles. Many genes have more than two alleles and are called Multiallelic Traits.

 2 alleles affect the phenotype equally & separately  not blended phenotype  human ABO blood groups  3 alleles  I A, I B, i  I A & I B alleles are co-dominant  glycoprotein antigens on RBC  I A I B = both antigens are produced  i allele recessive to both _____________________________

ABO BLOOD GROUP SYSTEM Type A Type B

Genetics of Blood type pheno- type genotype antigen on RBC antibodies in blood donation status AI A I A or I A i type A antigens on surface of RBC anti-B antibodies __ BI B I B or I B i type B antigens on surface of RBC anti-A antibodies __ ABI A I B both type A & type B antigens on surface of RBC no antibodies universal recipient Oi ii i no antigens on surface of RBC anti-A & anti-B antibodies universal donor

Polygenic traits  Some phenotypes determined by additive effects of 2 or more genes on a single character  phenotypes on a continuum  human traits  skin color  height  weight  eye color  intelligence  behaviors

_____________________________  Most genes are pleiotropic  one gene affects more than one phenotypic character  1 gene affects more than 1 trait  dwarfism (achondroplasia)  gigantism (acromegaly) Pleiotrophy

Achondroplasia  Dominant Allele  Over production of Fibroblast growth factor receptor 3. This prevents the formation of bone from cartilage.

Inheritance pattern of Achondroplasia aa A a Aa A a Aa aa Aa 50% dwarf:50% normal or 1:1 AA aa Aa 67% dwarf:33% normal or 2:1 Aa Aa x aaAa x Aa dominant inheritance dwarf lethal

Acromegaly: André the Giant

Acromegaly  Tumor formation in the pituitary gland  Familial acromegaly  In rare cases a gene on chromosome 11 believed to cause the formation and growth of an HGH-secreting tumor in the pituitary gland  can also cause tumors in other areas of the body  the parathyroid gland, which controls the amount of calcium in the bloodstream  the pancreas, which regulates insulin needed for the body to process

Epistasis  the effect of one gene being dependent on the presence of one or more “modifier genes” or  the interaction between two or more genes to control a single phenotype  called an epistatic gene  Ex.  fur color is mice  color in Labrador retrievers

_____________________________ B_C_ bbC_ _ _cc How would you know that difference wasn ’ t due to random chance? Statistical Analysis!  One gene completely masks another gene  coat color in mice = 2 separate genes  C,c: pigment (C) or no pigment (c)  B,b: more pigment (black=B) or less (brown=b)  cc = albino, no matter B allele  9:3:3:1 becomes 9:3:4

Epistasis in Labrador retrievers  2 genes: (E,e) & (B,b)  pigment (E) or no pigment (e)  pigment concentration: black (B) to brown (b) E–B–E–bbeeB–eebb

enzyme Skin color: Albinism Johnny & Edgar Winter albino  However albinism can be inherited as a single gene trait  aa = albino melanin = universal skin pigment tyrosine melanin albinism

 In humans & other mammals, there are 2 sex chromosomes: X & Y  2 X chromosomes  develop as a female: XX  gene redundancy, like autosomal chromosomes  an X & Y chromosome  develop as a male: XY  no redundancy Sex Determination XY X X XX XY 50% female : 50% male XX

Sex Linked Traits  Genes are on sex chromosomes  as opposed to autosomal chromosomes  first discovered by T.H. Morgan at Columbia U.  Drosophila breeding  good genetic subject  prolific  2 week generations  4 pairs of chromosomes  XX=female, XY=male 1910 | 1933

autosomal chromosomes sex chromosomes Classes of chromosomes

F 2 generation 100% red-eye female 50% red-eye male 50% white eye male Discovery of sex linkage P X F 1 generation (hybrids) 100% red eye offspring true-breeding white-eye male true-breeding red-eye female

Doesn’t work that way! RRrr What’s up with Morgan’s flies? x rr R R Rr 100% red eyes Rr x F1 Generation Rr R r RR Rrrr Rr 3 red : 1 white

BINGO! XRXRXRXR XRYXRY XRXRXRXR XrYXrY What’s up with Morgan’s flies? x XrXr Y XRXR 100% red eyes XRXR x XRXrXRXr XRYXRY XRXR Y XRXR XrXr 100% red females 50% red males; 50% white males XRXrXRXr XRXrXRXr XRYXRY XRXrXRXr XrYXrY XRYXRY

Genes on sex chromosomes  Y chromosome  few genes other than SRY( sex-determining region Y)  sex-determining region  master regulator for maleness  turns on genes for production of male hormones  many effects = pleiotropy!  X chromosome  other genes/traits beyond sex determination  mutations:  hemophilia  Duchenne muscular dystrophy  color-blindness

 Sex-linked  usually means “On the X chromosome”  more than 60 diseases traced to genes on X chromosome Human X chromosome

Map of Human Y chromosome? < 30 genes on Y chromosome Sex-determining Region Y ( SRY ) linked Channel Flipping ( FLP ) Catching & Throwing ( BLZ-1) Self confidence ( BLZ-2) note: not linked to ability gene Devotion to sports ( BUD-E) Addiction to death & destruction movies ( SAW-2) Scratching ( ITCH-E) Spitting ( P2E) Inability to express affection over phone ( ME-2) Selective hearing loss ( HUH) Total lack of recall for dates ( OOPS) Air guitar ( RIF)

Genes on the Y Chromosome

Hemophilia Hh x HH XHYXHY XHXhXHXh XHXhXHXh XHXH XhXh XHYXHY Y XHXH sex-linked recessive XHXH Y male / sperm XHXH XhXh female / eggs XHXHXHXH XHXhXHXh XHYXHYXhYXhY XHXHXHXH XHYXHY XHXhXHXh XhYXhY carrierdisease

X Inactivation (Dosage Compensation) Interphase: Chromomes can’t be stained, but a dark-staining body is visible in the nuclei of cells of female mammals Barr Body: Inactive X Males have only one X chromosome and females inactivate one X chromosome so both have only one active X chromosome

Which X gets inactivated? One or other of X becomes inactivated in early development. Within each cell, which X becomes inactivated is random. As development proceeds, all cells arising by cell division after that time have same X inactivated. Female becomes a mosaic

Calico Cat Example In 64-cell embryos

Male pattern baldness  Sex influenced trait  autosomal trait influenced by sex hormones  age effect as well = onset after 30 years old  dominant in males & recessive in females  B_ = bald in males; bb = bald in females

Nature vs. nurture  Phenotype is controlled by both environment & genes Color of Hydrangea flowers is influenced by soil pH Human skin color is influenced by both genetics & environmental conditions Coat color in arctic fox influenced by heat sensitive alleles

Mapping the Distance Between Genes  Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome  Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency © 2011 Pearson Education, Inc.

 A linkage map is a genetic map of a chromosome based on recombination frequencies  Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency  Map units indicate relative distance and order, not precise locations of genes © 2011 Pearson Education, Inc.

Figure Chromosome Recombination frequencies 9% 9.5% 17% b cn vg RESULTS

Figure Mutant phenotypes Short aristae Black body Cinnabar eyes Vestigial wings Brown eyes Long aristae (appendages on head) Gray body Red eyes Normal wings Red eyes Wild-type phenotypes

Any Questions?