W7 Flashcards
- chromosomes contain (…)
- position on a chromosome is a gene (…)
- chromosomes contain genes
- position on a chromosome is a gene locus
what can happen on these gene locus
the alleles can either be of the wild type whereby the DNA has had no changes, or, it can be the mutant with a changed DNA sequence
- if the condition is recessive, lower case letters are used in notation
- a plus sign denotes both dominance and that it is the wild type
- after dna replication, the (…) on the chromatids are identical
- homologous chromosomes have the(…) but may have (…)
- after dna replication, the alleles on the chromatids are identical
- homologous chromosomes have the same genes but may have different alleles
outline drosophila notation
- lower case, recessive is dominant
- upper case, dominant is dominant
- the one with the plus sign is dominant
note: in non drosophila species, there is no plus sign. also, the one with the capital letter is the dominant one
what are the genetic consequences of meiosis
anaphase 1:
- segregation of alleles
prophase 1:
- independent assortment of chromosomes whereby there is crossing over and recombination of alleles
what is complete dominance in terms of what it is, how it can be explained and monohybrid ratios
- a phenotype with a particular allele is dominant over another phenotype with another particular allele
- therefore in the heterozygote, dominant phenotype with particular allele shows it phenotype
segregation of alleles occurs at anaphase 1 and anaphase 2. the phenotype of the heterozygote can tell us the dominant phenotype
genotype: 1:2:1
phenotype: 3:1
what is incomplete dominance in terms of what it is, how it can be explained and monohybrid ratios
the heterozygote contains a intermediate phenotype between the homozygotes
how can it be explained?
- a biochemical pathway exists for the genes of the two homozygotes
1. A —–(enzyme 1)(allele Cr)—– > red pigment
2. A —–(enzyme 2)(allele Cw)—– > no red pigment
CrCr- 2 units of red pigment
CrCw- 1 unit of red pigment= pink
CwCw- 0 units of red pigment= white
the monohybrid ratio:
1:2:1 for genotype
1:2:1 for phenotype
whereby the 2 is for heterozygotes
what is codominance in terms of what it is, how it can be explained and monohybrid ratios
the full effects of both alleles can be seen in the phenotype of the heterozygote
it can be explained through an example of Sickle cell anaemia
- HBA/HBA have only normal RBC
- HBS/HBS only have sickled RBC
- HBS/HBA have unstable disintegrates consisting of some normal and some sickled RBC
+ this could be detected through a blood smear
the monohybrid ratio:
1:2:1 for genotype
1:2:1 for phenotype
whereby the 2 is for heterozygotes
describe the process of segregation of alleles in anaphase 1
- alleles on chromosomes are segregated so that the pairs of homologues go into seperate cells
- we expect that each combination is equally likely
describe the process of segregation of alleles in anaphase 2
- splitting of centromeres
- seperation of chromatids so now we have chromosomes\
- duplication of each type of gamete
describe extensions to mendel in terms of multiple alleles
mutations allow multiple alleles to be available, but only one pair can be expressed eg. one locus can have 4 alleles
describe extensions to mendel in terms of pleiotropy
a single gene may affect many features of the phenotype eg. sickle cell has affects over various organs ih the body
- this can be autosomal dominant eg. Marfan syndrome
describe extensions to mendel in terms of phenocopy
a copy of an inherited conditions but results from environmental factors
- the environment modifies the phenotype to mimic effects of specific genotypes eg. meromelia
describe extensions to mendel in terms of variable expression
degree of range in which a particular phenotype expressed by individuals, could be autosomal dominant eg. polydactyly
phenotype = genotype + environment
describe extensions to mendel in terms of reduced penetrance
same genotype, some not expressed at all eg. all people with HD express HD
eg. also polydactlyl
phenotype = genotype + environment
reduced penetrance is the extreme form of variable expression
describe extensions to mendel in terms of lethality
refers to changes in genotype/phenotype ratios
- an allele/genotype or mutation which results in death
- dominant or recessive
recessive:
- carries on because hetero survives
- affects those that are AA or Aa
- can be a dominant phenotype
dominant:
- neither AA or Aa survive
what is the effect of environment on sex determination
- location: eg. in bonellia, it is male if it lands near the proboscis
- temperature: this influences the percentage of males and is shown In various reptiles (lizards, alligator, turtles)
- in turtles, it influences a biochemical pathway whereby temperature changes the amount of the enzyme aromatase which leads to production of oestrogen
what is the effect of environment on sex determination in drosophila
- a particular genotype may change the expected sexual phenotype
- tra+ tra+ XX= female, tra+ tra+ XY= male
- tra+ is required for normal female development, tra= mutant allele at the transformer locus
tra tra, XX phenotypically male
tra tra XY male, no change - the tra locus can reverse the sex of a female
what is the effect of genes on sex determination
eg. disorder of sexual development (DSD)
human: androgen insensitivity locus on the X chromosome
- AR* is the androgen receptor mutation
- males XAR* Y appear as females
- from pedigree we see that it does not affect daughters and only the sons will have the female phenotype
androgen insensitivity:
- XY individuals produce testosterone but cells insensitive to it because of defect in testosterone:androgen receptor
- outwardly female, but not uterus, Fallopian tubes, ovaries have undescended testes
what is the effect of haplo/diploidy in sex determination
eg. Hymenoptera, honey bee
- female bees(workers and queen) are 2N, arising from fertilised eggs. these are heterozygous at a particular highly polymorphic locus
- male bees (drones) are N- arise from unfertilised eggs, homozygous at the locus
- queen 2N, so can be homozygous dominant or homozygous recessive or heterozygous
- male N so can have only one allele at each locus=hemizygous
- the male dies after mating, endophallus rips open the body cavity
what is the effect of sex chromosomes and autosomes
eg. drosophila
- sex is determined by the ratio of X chromosomes: sets of chromosomes A
- drosophila diploid, so has 2 sets of autosomes, 2A
- X/A = 1, female
- X/A = ½, male
normal males are AA XY, so 1X/2A=½, however AAX is also a male since 1X/2A=½, but sterile
- the Y chromosome is needed for fertility
what is the effect of sex chromosomes and autosomes in reference to a particular gene and protein
in drosophila, females have the sxl protein meaning they can switch on the tra protein
- males do not have the sxl protein and therefore cannot produce the tra protein
- this is because females have a higher chance of a homo dimer which can act as a TF for which the SXL protein is on
- males are more likely to have heterosexual dimers meaning the gene is not switched on
- ratio 1= female
special cases:
- XXY, AA. 1. female
- XXX, AA, 3/2. meta female that is sterile
- XXY, AAA. ⅓. meta male that is sterile
what is the effect of chromosomes on sex determination
non disjunction in males/females and fertilisation can affect the male and female phenotype whereby non disjunction can occur in anaphase 1 or 2
note: cells without chromosomes die and whilst there is still replication of DNA but there is no cytoplasmic division
note: only cells with an X can survive
aneuploidies in humans:
- 7.5% of all birth defects relate to disorders of sexual development
- 1/4500 children born with a significant DSD from ambiguous genitalia to complete sex reversal
eg. turners, klinefelters, triple X, XYY
what is turners syndrome
- X
- 1-2% pf all conceptions are turner
- only 1% survive to a live born infant
- it tells us how 2 SEX CHROMOSOMES IMPORTSNT FOR INTRAUTERINE GROWTH
- NOT RELATED TO THE age of mother or father
- however, 70-80% result from a sperm that had lost a sex chromosome
what is triple X syndrome
47, XXX
- typically taller than average but not other physical features
- normal sexual development and able to conceive children
- increased risk of learning disabilities, delayed development of speech and language skills, delated development of motor skills, hypotonia, behavioural and emotional difficulties are possible, seizures
- kidney abnormalities occur about 10% of affected females
FEMALES
note: XXXX
- IQ with mean of 55 speech and language delays behavioural problems
what is XYY
in MALES
- males are aggressive, tall and low IQ
- remember the trial cases and acquition
- mental retardait on and antisocial behaviour
- emotionally immature and have impulsive behaviour
what does the Y chromosome do?
- responsible for producing a testis
- femaleness is the result of not inheriting the Y chromosome
up to 6 weeks gestation, there is a mass of tissue which is undifferentiated, when the Y chromosome is resent, TDF (testis determining factor) IS EMPLOYED to produce the testis. when there is no Y chromosome, then the ovary is produced; by the 12th week, oogonia begins meiosis in female. 25th week arrested in meiosis until puberty
what does the testis determining factor do?
transcription factor: regulatory factor which binds to other genes to promote their expression
DAX 1- anti testis factor so SRY has to close this down
SOX9- on chromosome 17, when activated leads to differentiation of cells, and then, seminiferous tubules of the testis
outline the evidence to which TDF is testis determining
- XY females deletion of TDF
- XX males: insertion of Y chromosome with TDF locus, develops into male
- transgenic mice- took XX embryo and inserted TDF DNA sequence
describe the sex determination process
- undifferentiated gonads at 5-6 weeks are in the medulla and cortex
- the cortex is controlled by the SRY gene to produce a male and acts on the testes.
A. the testes produce AMH and testosterone.
B. whilst AMH inhibits the malarian ducts from production of internal genitalia such as the Fallopian tubes, uterus and proximal vagina,
C. testosterone becomes dihydrotestosterone through enzyme 5ALPHA reductase to produce external genitalia of penis and scrotum. testosterone also acts on the wolffian ducts to produce internal genitalia such as the epididymis, seminal vesicles and vas deferens - the medulla controls ovaries. the ovaries produce oestradiol which leads to androgen insensitivity, whereby its mutation means it is insensitive to the effects of testosterone and will not produce external genitalia. it will produce the external female genitalia such as the clitoris, labia and distal vagina
describe differentiation of the bipotential gonads
the biopotential gonads have both the wolffian ducts and the mullein duct. to produce a male, there needs to be MIF/AMH and Insl3, insulike like 3 descent of testes
describe 5 alpha reductase deficiency
autosomal recessive
- reduced levels can results in ambiguous genitalia
whereby testosterone produced by the testes cannot become dihydrotestosterone due to the deficiency of converting enzyme 5 alpha reductase. thus, no external genitalia of penis and scrotum
what is pseudohermaphroditism
children appear female- like until puberty. changes to male at puberty with surge of testosterone and hence dihydrotestosterone. this is an autosomal recessive with sex limited expression
list diseases of interest on the X chromosome
- Duchenne muscular dystrophy
- androgen receptor
- HMA
- colour blindness with alleles C and c
note: X much larger than Y
compare the x and y chromosome
- have homologous regions: these are called pseudo-autosomal region pairs in meiosis (this is a false autosomal region)
- genes on Y expressed only in the testis deletion or mutation may result in infertility. This is TDF in SRY (sex determining region of Y) - X-165Mb, Y-60Mb
describe crossing over with reference to a particular protein for X and Y chromosomes
The TDF region is usually on the Y chromosome, however, crossing over is not exact resulting in the TDF locus being transferred to X.
- this relates to XX males, XY females and transgenic mice where XX males gain TDF, XY females lose TDF and transgenic mice have TDF implanted
- THUS, genes on Y expressed only in the testis deletion or mutation may result in infertility
contrast heterogametic and heterogametic with reference to examples
homogametic refers to being all X, this is in females in humans
- heterogametic refers to there being two types of gametes that can be produced from this type of individual, for human males and drosophila, XY, XO(grasshoppers)
this is also shown in birds, some fish and butterflies
what is sex linkage and make reference to an example
- an allele for a particular trait is linked to a chromosome and is passed on during reproduction
- colourblindness
+ 8% of Australian males are colour blind - x sex linkage demonstrates that males are hemizygous
- hemizygous: Describes the genotype of a XY male or ZW female for an X or Z linked trait
things to note:
- if male gets trait, it is from the mother
how does one test the presence of a sex linkage and how does one go about undertaking this test?
- the reciprocal cross is used to determine if a gene locus is on a sex chromosome
- if a locus is on a sex chromosome the phenotypic ratio in the offspring of the reciprocal cross will be different, or else, it would be autosomal
how to make a reciprocal cross?
- female with phenotype A WITH male phenotype B
- female with phenotype B WITH male phenotype A
- the crosses will have different outcomes
THIS IS IN HMA
list x linked traits in humans
X linked recessive:
- colour blindness
- hma
- Duchenne muscular dystrophy
- fragile X
drosophilia- white eye
what is HMA
- x linked recessive
Haemophilia A- deficiency of factor 8, severe impairment in clotting
- 7 times more common
Haemophilia B- deficiency of factor 9, Christmas disease, mid impairment of clotting
why bad?
- platelet aggregation and secretion of co factors needed for clotting reactions
- conversion of inactive factor 12 t active factor 12
- platelet aggregation and secretion of co factors needed for clotting reactions
- blood clot consists of fibrin and cells
- mian issue: spont. bleeding
Queen Victoria
how can fragile X be detected
- visible when cells cultured in folate deficient thymidine deficient medium
- mutation is an expansion of a triplet repeat CGG
- stable repeat is between 6-54
- unstable 200-1000+
describe the gene for fragile X
- the mutation is an expansion in a CGG repeat in the FMR gene (Fragile X mental retardation protein). the repeat is in a part of the gene associated with regulation of expression
- stable repeat is between 6-54
- unstable 200-1000+
- between 53-200 is called pre mutation
FMRP regulatory protein which functions in neurons and dendrites
the expansion results in non protein because it disrupts transcription and translation
