W7

Question 1

• chromosomes contain (…)

- position on a chromosome is a gene (…)

Answer 1

• chromosomes contain genes

- position on a chromosome is a gene locus

Question 2

what can happen on these gene locus

Answer 2

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

Question 3

• after dna replication, the (…) on the chromatids are identical
• homologous chromosomes have the(…) but may have (…)

Answer 3

• after dna replication, the alleles on the chromatids are identical
• homologous chromosomes have the same genes but may have different alleles

Question 4

outline drosophila notation

Answer 4

• 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

Question 5

what are the genetic consequences of meiosis

Answer 5

anaphase 1:
- segregation of alleles

prophase 1:
- independent assortment of chromosomes whereby there is crossing over and recombination of alleles

Question 6

what is complete dominance in terms of what it is, how it can be explained and monohybrid ratios

Answer 6

• 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

Question 7

what is incomplete dominance in terms of what it is, how it can be explained and monohybrid ratios

Answer 7

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

Question 8

what is codominance in terms of what it is, how it can be explained and monohybrid ratios

Answer 8

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

Question 9

describe the process of segregation of alleles in anaphase 1

Answer 9

• alleles on chromosomes are segregated so that the pairs of homologues go into seperate cells
• we expect that each combination is equally likely

Question 10

describe the process of segregation of alleles in anaphase 2

Answer 10

• splitting of centromeres
• seperation of chromatids so now we have chromosomes\
• duplication of each type of gamete

Question 11

describe extensions to mendel in terms of multiple alleles

Answer 11

mutations allow multiple alleles to be available, but only one pair can be expressed eg. one locus can have 4 alleles

Question 12

describe extensions to mendel in terms of pleiotropy

Answer 12

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

Question 13

describe extensions to mendel in terms of phenocopy

Answer 13

a copy of an inherited conditions but results from environmental factors
- the environment modifies the phenotype to mimic effects of specific genotypes eg. meromelia

Question 14

describe extensions to mendel in terms of variable expression

Answer 14

degree of range in which a particular phenotype expressed by individuals, could be autosomal dominant eg. polydactyly

phenotype = genotype + environment

Question 15

describe extensions to mendel in terms of reduced penetrance

Answer 15

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

Question 16

describe extensions to mendel in terms of lethality

Answer 16

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

Question 17

what is the effect of environment on sex determination

Answer 17

1. location: eg. in bonellia, it is male if it lands near the proboscis
2. 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

Question 18

what is the effect of environment on sex determination in drosophila

Answer 18

• 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

Question 19

what is the effect of genes on sex determination

Answer 19

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

Question 20

what is the effect of haplo/diploidy in sex determination

Answer 20

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

Question 21

what is the effect of sex chromosomes and autosomes

Answer 21

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

Question 22

what is the effect of sex chromosomes and autosomes in reference to a particular gene and protein

Answer 22

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

Question 23

what is the effect of chromosomes on sex determination

Answer 23

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

Question 24

what is turners syndrome

Answer 24

• 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

Question 25

what is triple X syndrome

Answer 25

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

Question 26

what is XYY

Answer 26

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

Question 27

what does the Y chromosome do?

Answer 27

- 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

Question 28

what does the testis determining factor do?

Answer 28

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

Question 29

outline the evidence to which TDF is testis determining

Answer 29

- 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

Question 30

describe the sex determination process

Answer 30

1. undifferentiated gonads at 5-6 weeks are in the medulla and cortex 2. 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 3. 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

Question 31

describe differentiation of the bipotential gonads

Answer 31

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

Question 32

describe 5 alpha reductase deficiency

Answer 32

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

Question 33

what is pseudohermaphroditism

Answer 33

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

Question 34

list diseases of interest on the X chromosome

Answer 34

- Duchenne muscular dystrophy - androgen receptor - HMA - colour blindness with alleles C and c note: X much larger than Y

Question 35

compare the x and y chromosome

Answer 35

1. 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) 2. X-165Mb, Y-60Mb

Question 36

describe crossing over with reference to a particular protein for X and Y chromosomes

Answer 36

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

Question 37

contrast heterogametic and heterogametic with reference to examples

Answer 37

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

Question 38

what is sex linkage and make reference to an example

Answer 38

- 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

Question 39

how does one test the presence of a sex linkage and how does one go about undertaking this test?

Answer 39

- 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

Question 40

list x linked traits in humans

Answer 40

X linked recessive: - colour blindness - hma - Duchenne muscular dystrophy - fragile X drosophilia- white eye

Question 41

what is HMA

Answer 41

- 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? - 1. platelet aggregation and secretion of co factors needed for clotting reactions 2. conversion of inactive factor 12 t active factor 12 - blood clot consists of fibrin and cells - mian issue: spont. bleeding Queen Victoria

Question 42

how can fragile X be detected

Answer 42

- 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+

Question 43

describe the gene for fragile X

Answer 43

- 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