Lecture 10: Genes, Chromosomes, and Human Genetics Flashcards
What makes you who you are
- your genes; found on chromosomes
Modifications to Mendelian Genetics
- genetic linkage
- sex-linked genes
- chromosomal alterations
- non traditional patterns of inheritance
1) Genetic Linkage
define genes
genes
- sequences of nucleotides in DNA
- arranged Linearly in chromosomes (we have thousands on 1 chromosome)
Do all genes assort independently
- not necessarily, even though in mendels work all 7 characters did
- some genes are inherited together because they’re on the same chromosome (2 diff genes on 1 chromosome)
- Mendel never saw this because he didn’t pick Linked genes
Linked Genes
- genes on 1 chromosome
- linked during transmission from parents to offspring (passing entire chromosome to gamete)
- inherited like single genes
Break Linkage:
- prophase 1 (meiosis 1)
crossing over: enzymatic cut and pasting can break them
Drosophila Melanogaster
Fruit Fly
- model organism for animal genetics
- compared to Mendel’s Peas
- Morgan: first genetic map
- Used to test linkage and recombination (how we unlink genes)
linkage maps= of a chromosome
- relative location of genes
How far apart genes are on a chromosome will determine
degree of linkage if they’re linked
- closer 2 genes are they more linked because the chance of crossing over decreases (crossing over unlinks)
Gene Symbolism
normal alleles (wild-type)
- usually most common allele
- designated by + symbol (wild-type common)
- usually dominant
FRUIT FLIES:
wild-type:
pr+=red eyes
vg+=normal wings
mutant:
pr=purple
vg=vestigial wings
Genetic Recombination
how will it occur?
- alleles linked on same chromosome exchange segments between homologs chromosomes
- exchanges occur while homologs chromosomes pair during Prophase 1
Experimental Evidence for Gene Linkage
Q: do purple-eye vestigial wings (pr vg) assort independently?
A: Morgan crossed wild breed with purple vestigial wings, F1 were all wild breed (dominant), then did a testcross with F1 generation and didn’t get 1:1:1:1
- HENCE NO INDEPENDENT ASSORTMENT, they’re linked
- principle of independent recombination
Recombination Frequency
- amount of recombination between 2 genes that reflects the distinct between them
- the greater the distance the greater the recombination frequency
= greater chance of crossover btwn genes
Linkage maps of chromosomes
- recombination frequencies used to determine relative borders on a chromosome
- linkage map for genes a,b, and c
8% recombination f=8 map units apart between gene a and c
a (—-8%) c (—2%) b
total: 9.6%, because its an underestimation (because of double crossing over) the real f combined is 10%
therefore 1 map unit=1% recombination
Single vs Double Crossing Over
single: two chromosomes exchange info at 1 point, leading to swapping of genes
( chromosome A has genes A1 and A2 and B has B1 and B2
leads to A1B2 and A2B1)
double: two different exchange events occur at 2 points on chromosome, more variety and combos
(so we can get more variation A1B1 and A2B2)
BECAUSE OF DOUBLE CROSSING OVER:
= sometimes the chromosome can look the same as it did before crossing over so we think 0 crossing over happened or less crossing over happened=underestimation
Can genes on the same chromosome ever assort independently
- widely separated linked genes often recombine
- seem to assort independently
- detected by testing linkage to genes between them
- Mendel looked at genes on separate chromosomes OR they were linked but so far apart that they behaved separately *
= at 50+ mpu the 2 genes behaved as if they were on 2 separate chrosomes - hence principle of independent assortment
Why only 50% or 50 MPU MAX?
(only half of the offspring show new genetic combos because of crossing over)
- double crossing over can result in the restoration of the original parental combination of alleles
- difficult to tell whether genes are on the same chromosome or not
- inheritance pattern will appear as if they are assorting independently as if they were on diff chromosomes, 50% marks this point
- double
2) Sex Linked Genes
- sex chromosomes determine sex
X and Y chromosomes in many species
XX: woman
XY: man - other chromosomes are called autosomes
Human Sex chromosomes
- Human X chromosome
*large=2350 genes (some determine sex, most determine nonsexual traits)
-many X-linked genes are nonsexual traits - Human Y chromosomes
- small (few genes)
- very little homology with X chromosome
- contains SRY gene (8 weeks post-fertilization)
- regulates expression of genes that trigger male development (females have 0 deviation)
OG DEVELOPMENT PATHWAY
- females continue
- males deviate (SRY gene)
Sex Linkage
Female (XX) 2 copies of X linked alleles
- heterozygote recessive: allele hidden (carrier)
- homozygote recessive: trait is expressed
Male (XY): 1 copy of X-linked allele, only males have Y-linked alleles
- 1 copy of a recessive allele results in expression of the trait
Eye Colour In fruit flies
-Morgans work
- Normal wild-type: RED
- Mutant: WHITE
(sex-linked)
how was the white-eye inherited?
P: RED (female) x WHITE (male)
F1: ALL RED (therefore, white is recessive)
- follows mendels laws so far…
F2: all red-eyed females,
1/2 red eyed and 1/2 white eyed males
=3/4 red;1/4 whites
= 3:1 RATIO
- female: 1:0
- male: 1:1
RECIPROCAL CROSS
- Morgan flips it to determine if sex has any influence!
P: WHITE (female) X RED (male)
F1: Females have red eyes, and males have white eyes (therefore, its X-Linked gene)
F2: he wasn’t seeing 3:1
- ratio amongst general population doesn’t line up with sex based ratio
NEW RATIO: female: 1:1
male: 1:1
1/2 red, 1/2 white
Human Sex-Linked genes
whats more common 4 males
- X-Linked recessive traits are more common in males
1) red-green colour blindness
2) hemophilia: defective blood clotting protein=mutation - Seen more commonly because they only have 1 X, females need both Xs to match to acquire a trait *
Pedigree
- show genotypes and phenoytpe
- X-Linked
1 X chromosome Inactivation
- DOSAGE COMPENSATION
- in female mammals, inactivation of 1 X chromosome in each cell makes the dosage of X-linked genes the same smalls
- Occurs during embryonic development
- because the condensation of chromosomes makes them so tight and inactivates them, its hard for them to be expressed because condensation prevents transcription/translations *
Barr Body
- Random Inactivation of either X chromosome by condensation
- Attached to side of nucleus
- Copies during mitosis but always inactive
- Results in patches of cells with different active X chromosome
Calico Cats
- Heterozygote Female (RARE to be Male)
if cat has xxi it can be male
Dominant O gene is expression turns B off
or!
Expressed; the O is mutant recessive, B is not turned off
Creates patches of orange and black fur on cat
orange: determined by inactivation of X
black: NOT determined by inactivation of X (determined by expression of O gene)
Therefore, O gene is EPISTATIC to B gene
- turning it (B) off prevents melanin deposition hence ORANGE FUR
- expression of the O gene will ctrl expression of the B gene to either produces melanin (black patch) or turning it off (orange fur)
- Chromosomal Alteration
- Deletion: broken segment lost from chromosome
missing segment contains genes that are essential for normal development or cellular functions - Duplication: broken segment inserted into homologs chromosome
- on exact same chromosome
one copy can mutate into new forms w/o srsly affecting the basic functions of organism - Translocation: broken segment attached to nonhomologus chromosome
- can also exchange DNA by accident
**generally reciprocal, so 2 non-homolgous chromosomes exchange segments, resembles genetic recbomination but the 2 chromosomes involved dont contain the same genes*
most cancers are this - Inversion: broken segment re-attached in reversed orientation (put in backwards)
When does chromosomal alteration occur
prophase 1
- to be inherited must occur in cells giving rise to sperm and egg
Reciprocal Translocation of CML
CML- cancer of leukocytes
- translocation of chromosomes 9 and 22
- nonhomologus but they still recombined
ABL gene: next to BCR gene it becomes overactive
- codes for tyrosine kinase (add PO4 to Try a.a. to target protein)
- Cells grow out of ctrl
(cell response on chromosome a, the gene is very regulated but the gene is swapped to chromosome 22 causing deregulation = increased production of Tyr Kinase)
Gleevac- drug that inhibits tyrosine kinase
Inhibits Kinase-enzyme for tyrosine
1) a piece of chromosome 9=ABL fuses with a piece of chromosome 22=BCR, which will create the gene on chromosome 22
2) BCR-ABL on chromosome 22 will code for an abnormal tyrosine kinase, its always active leading to out of ctrl growth
3) gleevac target the BCR-ABL tyrosine kinase to block abnormal signalling of out of ctrl growth
Nondisjunction
- Failure of homologs pair separation during Meiosis 1
- Failure of Chromatid separated during Meiosis 2 (mislivision)
(NONDISJUNCTION) - Cells with too many or too little chromosomes deal with the failure to properly separate into hc in meiosis 1 and sc in meiosis 2)
What does nondisjunction produce
MEIOSIS 1: 4 GENETICALLY ABNORMAL CELLS
- 1/4 too many
- 1/4 too little
- 1/2 just right
MEIOSIS 2: 2 GENETICALLY ABNORMAL CELLS
Changes in Chromosome Number
euploids:
- normal number of chromosome
aneuploids:
- extra or missing chromosomes in a cell
polyploids:
- extra set of chromosomes (triploids)
- spindle fails during cell division
* spindle fails to seperate the duplicated chromosomes which are therefore incorporated into a single nucleus w/ twice the usual number of chromosomes*
Aneuploids
- abnormalities usually prevent embryo development
- in animals: lethal before birth
- in humans: 25% of miscarriages during trimester 1 occur because of this
Exception in humans is Down syndrome:
- Three copies of chromosome 21
- Physical and learning difficulties (but usually long life, caused by failure to separate hc during gamete formation more common in females)
- frequency of nondisjunction increases as women age
Down syndrome and genetic testing
- genetic testing can tell us the likelihood of this happening
Aneuploidy of Sex Chromosome
OO x Y sperm: YO (NOT VIABLE)
- will die bc w/o any X chromosome you’re missing over 2300 genes that determine important characteristics
XO x X sperm: XO (TURNER SYNDROME)
- 1 X
- Undeveloped female reproductive system
XX x Y sperm: XXY (KLINEFELTER SYNDROME)
- biologically male may have undeveloped or remnants of female reproductive parts
- male calcite cats would be XXY
XX x X sperm: XXX (TRIPLE X SYNDROME)
- biologically female
- no shown symptoms because 2/3 Xs will inactivate showing no phenotype of that, only way you’d know is via karyotype
Polyploids
Common in plants
- polyploidy often hardier and more successful
- source of variability in plant evolution
Uncommon in animals
- usually has lethal effects during embryonic development
- won’t even get past early developmental stages
therefore, animals have a different system compared to plants
Modes of Inheritance
1) autosomal recessive inheritance
2) autosomal dominant inheritance
3) X-linked recessive inheritance
4) Nontraditional patterns of inheritance
1) Autosomal Recessive Inheritance
- Males or females carry a recessive allele on an autosome
Ex. Cystic Fibrosis, albinism, sickle cell
Heterozygote: don’t show trait, they can put it on though
- Carrier
- No symptoms
Homozygote Recessive
- shows symptoms of trait
2) Autosomal Dominant Inheritance
Therefore, if you’re homozygous dominance or heterozygous you’ll show symptoms of traits if you’re homo recessive you’ll be normal
Dominant gene is carried on an autosome
Homozygote dominant (abnormal trait) or heterozygote
- show symptoms of the trait
Homozygote Recessive
-Normal
EX. ACHONDROPLASIA- type of dwarfism
-people who don’t have it are homo recessive, so to not be a dwarf you have the 2 recessive genes
=autosomal dominant allele on a chromosome
3) X-Linked Recessive Inheritance
Recessive allele carried on X chromosome
*Males
- recessive allele on X chromosome
- show symptoms
*Females
- heterozygous carriers, no symptoms
- homozygous, show symptoms
Ex. Colour blindness and Hemophilia
Genetic Counselling Techniques
TRYING TO DETERMINE PROBABILITY OF OFFSPRING HAVING A PARTICULAR DISORDER
Identification of parental genotypes
- construction of family pedigrees
1) Parental Diagnosis: tests cells
Cells obtained from
- embryo
- amniotic fluid around the embryo
- placenta
2) Postnatal Genetic screening
- biochemical and molecular tests
4) Nontraditional Patterns of Inheritance
- goes against Mendel’s Law (he never saw it)
a) cytoplasmic inheritance: follows the pattern of inheritance of mitochondria or chloroplasts
b) in genomic imprinting the allele is inherited from one of the parents, is expressed while the other is silent
Cytoplasmic Inheritance
- genes carried on DNA in mitochondria or chloroplasts
- cytoplasmic inheritance follows the maternal line
*zygotes cytoplasm originates from egg (and everything in there including mitochondrial and chloroplast DNA and organelles are transferred to the zygote *
Mutant alleles in organelle DNA
- Mendelian inheritance not followed
- Uniparental inheritance from females (dont segregate by meiosis)
Genomic Imprinting
Expression of an allele is determined by the parent that contributed it
- Only 1 allele (from either father or mother) is expressed
- Other allele is turned OFF (silenced) : IMPRINTED ALLELE
Often, result of methylation of region adjacent to gene is responsible for trait
= EPIGENETICS
-LOSS OF IMPRINTING LEADS TO DISORDERS
IgF2 gene (and genomic imprinting on mice)
Igf2- codes for insulin-like growth factor
Parental copy of lgF2 gene is active (expressed)
Maternal copy of lgF2 gene is imprinted (inactive)
SMALL MOUSE
a) a heterozygote inheriting a deleted lgf2 gene from the male parent develops into a small mouse
- dad gene turned off growth factor=small mouse
NORMAL MOUSE
a) heterozygote inheriting a deleted lgf2 gene from mom (because its alr imprinted and silenced)
b) homozygous for normal allele, parental allele is active and maternal allele is silenced
as long as normal allele is inherited from male parent=normal size
evolutionary explanation of IgF2 gene on mice
- Mom will feed mouse, so we imprint to prevent huge babies to ration food
- Doesn’t affect dad
- They can feed all offspring if smaller and have enough energy to produce more litter
Explain the processes of Prenatal Diagnosis
TWO WAYS:
1) Obtaining Cells from Amniotic Fluid
- centrifuged so cells are at bottom
- these are cells from the embryo (the baby’s cells)
- amniotic fluid is around the uterus
DANGER: CAN RUPTURE SAC (WATER BROKE) YOU DON’T WANNA DISRUPT BABY’S ENVIRONMENT
2) Placenta
- the placenta is an organ produced during pregnancy to help nourish baby made with its cells
Method you do depends on the mom’s age and how far along she is
Postnatal Genetic screening will only occur if the baby is already born (series of blood tests)
Methylation and genomic imprinting
- adding methyl groups will prevent expression
- nucleotide sequences and their modifications (methylation) can be inherited, depends on whether its mom or dads gene *
epigenetic
- takes environment into account
male calico cats
- can only exist if they have kleinfelter syndrome otherwise they will only be fully black or fully orange
process of calcio cats summarized:
- one X codes for orange and one X codes for black
= when one is inactivated it’s silenced but still appears in patches
an organism has many more genes than..
chromosomes
genes located on different chromosomes assort indpeendently during mieosis because….
the 2 chromosomes assort independently during meiosis because the 2 chromosomes behave independently of one another as they line up on the metaphase plate
parental gametes=simple segregation w/o crossing over
f1- cross over
f2- no crossing over, same as P
why do genes on the same chromosome tend to be inherited together in genetic crosses
(meaning they dont assort independently)
- because the chromosome is inherited as a single unit in meiosis
- = linked genes
it was once believed that they had to have been on the same chromosome
they dont really have to as long as they are close enough to eachother 4 no crossing over
genetic map
- shows the relative order of genes on a chromosome
- estimates the distance seperating genes
*genes sitting far apart would be more likely to be seperaated from one another during meiotic crossing over (prophase 1) than genes lying closer together, therefore all offspring are guaranteed to have one recessive allele from each locus
any change from wild-type
=mutant
Antp+ refers to …
knowing…
Antp=dominant mutant allele
+=wild type
Antp+ refers to recessive allele giving a wild-type phenotype when homozygous
- dominant would only b for heterozygous
F2 offspring are the ones that inherit chromosomes that were….
- NOT involved in recombination in the dihybrid parent
therefore, parental offspring dont always resemble F1 parents of cross
they will mostly
measure of distance seperating genes
relative frequency of recombinant offspring
- smaller the recombinants between two loci=closer the loci are to eachother along chromosome
phenotypes of offpsring directly reflect the genotype produced by
the dihybrid parent
a) what type of cross is used to discover whether 2 genes are linked or not
b) how can 2 genes be on the same chromosome and assort independently
c) if 2 genes assort independently how would you know whether they are on the same chromosome or not
a) test cross
- determine if they match whats expected from independent assortment or if they’re different
b) if they are far enough to prevent crossing over
c) if 50%=on 1 chromosome, if greater than 50% than theyre on different chromosomes
types of dosage compensation
- expression of genes on the single male X chromosome were doubled
- expression of genes on both female X chromosome were halved
- 1 X chromosome were turned off in females (what is observed in mammals)
INACTIVATION: occurs through condensation that folds and packs chromatin into a tight coiled state similar to condensed state of chromosomes during cell division
- occurs during embryonic development
- independent per organism, what X mom inactivates doesnt affect what X daughter inactivates (applies for identical twins too)
changes in chromosome structure or number
= source of atypical development and source of variability for evolutionary processes (esp polyploidy for plants)
T/F: failure of homolgoues to disjoin in meiosis 1 doesn’t affect meiosis 2
T
- chromatids will most likely seperate normally in meiosis 2
mechanisms responsible for
a) duplication of chromosomes segment
b) down syndrome
c) chromosome translocation
d) polyploidy
a) unequal crossing over (must occur in germline leading development of egg/sperm)
- homologus chromosome misalign
b) aneuploidy (nondisjunction)
(failure of chromosomes to seperate properly during meiosis)
c) chromosomal breakage
d) nondisjunction (entire sets)
autosomal recessive inheritance
- homozygous dominant: free of symptoms
- heterozygotes: free of symtpoms but are carriers
- homozygous recessive: show the trait
epigenetic mechanism
- alter expression of genes in ways that are stable, heritable but reversible
- during inheritance from parent to offspring w/o altering DNA sequence
how are X and Y chromosomes paired during meiosis
synaptonemal complex: as an XY body
- homologus chromosomes
