Chromosomes and their abnormalities

Question 1

Only have 23 nuclear chromosomes

Answer 1

Gametes- oocytes and sperm cells, have only 23 nuclear chromosomes (haploid)

Question 2

designate this karyotype

Answer 2

46,XY

Question 3

designate this karyotype for male or female

Answer 3

47,XY,+21 or 47,XX,+21

Question 4

designate the karyotype for robertsonian translocation downsyndrome

female and male

Answer 4

46,XX,rob(14;21), +21

46,XY,rob(14;21),+21

Question 5

designate the karyotype edwards syndrome for female and male

Answer 5

47,XX,+18 or 47,XY,+18

Question 6

designate patau karyotype

Answer 6

47,XX,+13 or 47,XY,+13

Question 7

designate the karyotype for cri du chat

Answer 7

46,XX,del(5p) or 46,XY,del(5p)

Question 8

designate karyotype for klinefelter syndrome

Answer 8

47,XXY

Question 9

designate the karyotype for turner syndrome

Answer 9

45, X and 45,X/46,XX mosaics

Question 10

what are the following types of chromosomes?

1. P and q arms are clearly different lengths
2. p and q arms are ~ equal lengths
3. centromere is near one end

Answer 10

1. submetacentric
   
   1. p and q arms are clearly different length
2. metacentric
   
   1. ~equal length of p and q arms
3. acrocentric
   
   1. centromere is near one end

Question 11

what is the segragation of sister chromatids?

Answer 11

disjunction

Question 12

abnormal chromosome seperation during meiosis

Answer 12

non-disjunction

Question 13

meitotic crossover ocurrs during what time of meiosis?

Answer 13

meitotic cell division - production of haploid gametes

1. meitotic crossover (genetic recombination)
   
   1. increases genetic diversity
2. occurs during meiosis1- P1

Question 14

describe autosomal deletion syndrome:

1. cause
2. type of cry
3. phenotypic expression

Answer 14

cri du chat

1. caused by deletions in the p arm of chromosome 5:
   
   1. 46,XX,del(5p) or 47,XY,del(5p)
2. cat like cry
3. phenotypic expression
   
   1. intellectual disabilities
   2. growth retardation
   3. speech impairment
   4. heart problems
   5. small head
   6. narrow eyes , with greater than normal distance between them
   7. low-set ears

Question 15

• what are the increases in incidence of edwards?
• what are the phenotypic expressions?

Answer 15

47,XX,+18

1. incidence increases with mother’s age
2. phenotypic expression
   
   1. intellectual disabillities
   2. failure to thirve
   3. congenital hear problems
   4. receding jaw
   5. low-set, malformed ear
   6. specifically clenching fist
   7. rocker-bottom feet

Question 16

what chromosomes are considered for uniparental disomy? generate a flow chart examplifying the act of the UPD

Answer 16

take notice that a phenotype may be rescued from a UPD

Question 17

what can be expected with most chromosomal abnormalities?

Answer 17

intellectual disabilities

developmental problems

cancers

Question 18

what are the types of chromosomal abnormalities?

Answer 18

1. abnormal chromosome number
2. structural abnormalities
   
   1. balanced
      
      1. normal complement of chromosomal material
         
         1. ex: uneaqual crossover between chromosomes
   2. unbalanced
      
      1. there is missing or additional chromosomal material
         
         1. deletions or insertions

Question 19

total chromosome number is not a multiple of 23. What are the two types? discuss the compatability for life.

Answer 19

aneuploid

1. trisomy
   
   1. abnormal (extra chromosome)
   2. most common:
      
      1. x
      2. 21
      3. 18
      4. 13
2. monosomy
   
   1. abnormal (missing chromosome)
   2. only turner syndrome patients are viable
      
      1. 45,X

Question 20

most common genetic cause of intellectual disability.

what 5 ways to generate this phenotype?

Answer 20

down syndrome

1. 47,XY,+21 or 47,XX,+21
2. 46,XX,rob(14;21),+21 or 46,XY,rob(14;21),+21
3. 46,XX,i(21q21q) or 46,XY,i(21q21q)
   
   1. isochromosome
   2. the logn arms of two chromosome 21s join together
4. 46,XX/47,XX+21 or 46,XY/47,XY,+21
   
   1. occurs during embryonic develeopment. some cells are wild type and others are downs
5. partial trisomy 21
   
   1. only part of chromosome 21 is present in triplicate
   2. one c’some is structural unbalanced

Question 21

describe the sex-specific differentiation and phenotypic sex, pertaining to gonadal development

Answer 21

• p arm
  
  • tetis dependent factor: expression of the SRY GENE ON THE Y CHROMOSOME induces male gonadal development
    
    • SRY is a transcription factor for TDF
  • very close to the telomeres and homologous region where gentic information between X and Y is shared
• q arm
  
  • makes sperm and other genes

Question 22

1. what is increases the incidence of patau
2. what are the phenotypic expressions

Answer 22

47,XX,+13

1. incidence increases with mothers age
2. phenotypic expression
   
   1. intellectual disabillities
   2. failure to thrive
   3. congenital heart problems
   4. sloping forehead
   5. cleft-lip
   6. polydactyly
   7. rocker bottom feet

Question 23

describe the normal crossover and abnormal structural transnlocation between sex chromosomes. generate the genetypes and phenotypes

Answer 23

1. Sex reversal-
   
   1. transfer of SRY from Y to X in sperm cells can produce XX male (gain of SRY) or XY female (loss of SRY) offsprings
2. loss of function mutations in SRY also produces XY female offspring

Question 24

What happens if there are more than one X c’somes in the human genome?

Answer 24

if more than two X c’somes are present, all but one will be inactivated.

If one of the X c’somes is aberrant (substandard), it will be preferentially inactivated

Question 25

what are 5 causes of sex reversals?

Answer 25

1. Transfer of SRY from Y to X in male gametes
   
   1. generates
      
      1. XX-male
      2. XY-female
2. loss of function mutations of SRY
   
   1. XY-female
3. DAX-1 gene duplication
   
   1. XY-female
4. SOX 9 loss of function mutation
   
   1. XY-female
5. SOX9 gene duplication
   
   1. XX-male

Question 26

what is the function of SRY, DAX1 and SOX 9 expression?

Answer 26

DAX 1 and SOX9 are transcription factors and their expression leveles determine gonadal development

1. SRY leads to SOX9 expression, which increases gonadal development
2. DAX1 and SOX9 compete for development, which ever is expressed more determines the sex.
   
   1. can cause sex reversal

Question 27

what ensures similar X gene dosage between males and females

Answer 27

x chromosome inactivation (Xi)

silencing the genes of one X chromosome to ensure simlar X gene dosage between males and females

Question 28

most of the unsilenced genes are on which side of the X c’some?

Answer 28

most unsilenced genes are on the distal end of the p arm (psudoautsomal region)

Question 29

describe the process of X inactivation

Answer 29

1. Inactivatio nis directed by the xinactivatio ncenter (XIC)** that is located on the **q arm of the X chromosome
2. XIC produces a large non-coding RNA (XIST)** that initiates changes in **histone composition and DNA methylation of the chromosome. This causes the inactivation of most of the genes.
3. X chromosome inactivation is not 100%
   
   1. some genes remain active even on the inactivated chromosome
   2. most unsilenced genes are on the distal end of the parm
4. Both X chromosomes are necessary for correct female sex development

Question 30

when does X inactivation occur?

Answer 30

random- occurs during early embryogenesis

daughter cells in mitosis inherit the Xi pattern

females are mosaic for X-linked gene expression

Question 31

What disease does a person have with the following karyotype? what phentypes are associated with this syndrome?

47, XXY

Answer 31

47,XXY = kleinfelter syndrome( most frequently)

48,XXXY is possible, but they are

1. tall
2. feminine statuure
3. hypogonadism (infertile)
4. some learning deficiencies

Question 32

what disease is associated with the following karyotype? describe the phenotype

45, X

Answer 32

45,X = turner syndrome

phenotype

1. webbed neck
2. edema
3. wide chest (man like)

Question 33

are there karyotypes of turner syndrome that are fertile?

Answer 33

yes,

• 45,X/46,XX mosaics

the rest are not

• 45,X
• 46X,i(Xq)
• 45,X/46,X,i(Xq) mosaics - but important genes are silenced

Question 34

How can a female contain two X chromosomes and still be daiagnosed with turner syndrome? Are these patients fertile?

Answer 34

• 46,X,i(Xq)
• i(Xq): isochromosome, that contains two long arms (q) of the X chromosome
  
  • formed by incorrect separation of sister chromatids during meiosis 2
• these patients are not fertile, because both X’s are necessary for proper female development, regardless of the inactivation important genes are still expressed in the pseudoautosomal region (and others)

Question 35

describe the disorder, sexual development, intelligence and behavior for the following karyotype

47,XXY

Answer 35

Klinfelter syndrome

• 47,XXY
• tall male
• infertile; hypogonadism
• learning difficulties (not all patients)
• may have poor psychosocial adjusment

Question 36

describe the disorder, sexual development, intelligence and behavior for the following karyotype

47,XYY

Answer 36

1. XYY syndrome
2. 47,XYY
3. tall male
4. normal
5. normal
6. frequent behavior problems

Question 37

describe the disorder, sexual development, intelligence and behavior for the following karyotype

47, XXX

Answer 37

trisomy X

1. 47,XXX
2. female, usually tall
3. usually normal
4. learning difficulties (not all)
5. occasional behavior problems

Question 38

describe the disorder, sexual development, intelligence and behavior for the following karyotype

45,X

Answer 38

turner syndrome

1. 45,X
2. short female, distinctive features
   
   1. webbed neck, edema, wide chest, short stature, streak gonads, can’t enter puberty, infertile
3. slightly reduced intelligence
4. rare behavioral problems