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Foundations Exam 1 > Genetics and Genomics > Flashcards

Flashcards in Genetics and Genomics Deck (66):
1

What is a haplotype?

=an individuals set of alleles at a locus or cluster or loci on a chromosome

2

What are single gene disorders?

-these disorders are determined primarily by the alleles at a SINGLE locus
-recurrence risk describes the likelihood of passing on the gene

3

Mendelian Genetics... what is it concerned with?

-monogenetic traits aka single gene traits

4

Independent assortment

is one gene locus is independently transmitted from a gene on a different locus

5

Autosomal dominant disease

seen in every generation
M=F
-structural genes are often seen in this inheritance pattern
-no skipping generations **unless new mutation!**
-probability to inherit=50%

ex. achondroplasia

6

Achondroplastics are...

rizomyere???

their limbs (humerus and femur) are short but their tib/fib and radius/ulna are normal length

7

What is the danger with 2 people who have an AD disease mating?

-they have more problems in those who will become homozygotes much more severe issues

8

Autosomal Recessive

-rare
-often seen in metabolic disorders
-this is sometimes seen in those who are relatives who mate CONSANGUINITY
-those that are heterozygotes may have reduced enzyme activity and then combine to make no activity
M=F
-probability to inherit from heterozygote parents 25%

Ex.
-Hurler/Hunter

9

What is hurler syndrome?

-AR disease
-skeletal abnormalities
-similar to hunter

10

Cystic fibrosis

-mutation to CTFR gene
-Cl transporter mutation
-pleiotropic: effects more than one organ

11

Remember that dominant and recessive refer to ___ not ___

traits not genes!

12

Sex linked inheritance

types:
X linked dominant
X linked recessive
Y linked

x chromosome: larger so more mutations
-common in men

y linked: much smaller contains less genes

13

X linked recessive

M > F--bc males usually only ones affected
-SONS of heterozygote mothers have 50% chance of being affected

14

X linked dominant

M and F can be affected
-all female offspring of affected father will be affected

15

Y linked

only father to son transmission

16

Mitochondrial Inheritance

-only given from mother
-all offspring of affected females show signs of disease
-not all mitochondria congregate in specific organs... so they effect organs different =heteroplasmy

17

New mutations

-this can complicate the "normal" pattern of inheritance
-the gene transmitted undergoes a mutation from the normal allele

18

Achondroplasia and risks and what they have!

-most cases are due to new mutations
-only 1/8 are transmitted from dwarf parents
-distinguish this by taking a family hx

remember they are: Rhizomelic---> refers to either a disproportion of the length of the proximal limb, such as the shortened limbs of achondroplasia, or some other disorder of the hip or shoulder.

19

What is gremlin mosaicism?

-when 2 or more offspring present with an AD disease with no familial hx
-this is when all parts of the germline cells are affected by the same mutation
-mutation occurs during the parents embryonic development of the germ cells

20

Age Dependent Penetrance

aka delayed age onset
-ex. of this is BRCA gene
-this is when the disease does not present until AFTER patients reach reproductive age or adulthood
-this can cause a difficulty in detecting the mode of inheritance

other ex.
huntingtons
polycystic kidney disease
alzheimers

21

Reduced penetrance

-this is when those that have the genotype fail to express the appropriate phenotype although they pass it to the next generation

penetrance is the general idea that a phenotype expression is dependent upon the predisposing genotype

ex. retinoblastoma

22

Variable expression

a trait in which the same genotype can produce phenotypes of varying severity or expression
-penetrance=complete
-severity is what varies
-a parent with midl expression may pass on the disease

ex. neurofibroblastoma

23

What are some causes for variable expression?

1. environmental factors
2. modifier genes
3. allelic heterogeneity

24

What is pleiotropy?

-genes that affect multiple aspects of physio or anatomy

ex. sickle cell
OI
CF

25

Marfan syndrome

-mutation to fibrillar

ex. of pleiotropy

26

Locus heterogeneity

=single disease phenotype caused by mutations at different loci in different families

a risk of this is testing for the wrong mutation
-ex. OI

27

Genomic Imprinting... ex. of this

=process by which genetic material is expressed differently when inherited from the mother than when inherited from the father

-methylation

ex. prader will an anglemans

Prader willi is inherited from the PATERNAL side
Anglemans is MATERNAL (heavy retardation)

28

Anticipation

=progressivle earlier onset and increased severity of certain diseases in successive generations of a family

ex. myotonic dystrophy

29

Population genetics: what factors determines it?

the branch of genetics dealing with genetic variation and genetic evolution of population
-it looks at how these frequencies change or are maintained in different populations

a. genetic factors
b. environmental and societal factors

30

What is the multiplication rule?

probability that BOTH event 1 and 2 will occur together

multiply probabilities together

31

What is the addition rule?

probability that EITHER event 1 or 2 will occur together

add the probabilities together

32

hardy weinberg

states that population frequencies will stay at a constant from generation to generation

p=normal
q=mutant
p+q=1
*calculates genotype frequencies

p^2 +2pq + q^2=1
p^2=homozygous normal

33

what are the assumptions for hardy weinberg to be true? 4

1. large population
2. no mutation
3. no selection
4. no migration

34

when is hardy weinberg used in the clinical setting?

often used for autosomal recessive conditions

35

what is the 2/3 rule?

2/3 for heterozygotes who are carriers and do not have disease. 1/4 chance for child who does not have the disease and multiple these by the population frequency

36

What are some causes in population change frequencies?

1. natural selection
2. genetic drift
3. founder effect
4. gene flow

37

natural selection... ex. of some diseases

-sickle cell: protects from malaria
-CF: protects against diarrhea
leiden V: entourage coagulation

38

What are some examples of the founder effect?

-the founder effect is a large shift in frequencies in a small population containing little genetic variation
-often subsets of populations
a. islands
b. small towns
c. ashkenazi jews

39

Why is knowing the ethnic population of your patient important for genetic testing?

-if you know the ethnic population you can order more specific genetic testing
-this can ultimately save cost

40

What is cytogenetics?

=the study of chromosomes and their abnormalities
-uses cytology and genetics

41

What is a karyotype? What criteria are they numbered by?

-chromosomes are extracted from nucleus, stained, and matched according to
a. size
b. banding patterns
c. location of centromere

42

nomenclature for chromosomes

p=petitie small arm
q=long arm

metacentric: equal on each side of centromere
submetacentric: longer on once side
acrocentric: very small p arm

43

What is the problem with acrocentric chromosomes?

they often can have robertsonian translocations

44

What is euploid?

a multiple of a haploid number (N=23)

45

What is aneuploid?

trisomy or monosomy
=extra or missing chromosomes
-it is the state of not having euploidy
**most common cause is nondisjunction**

46

When does nondisjunction occur?

it can occur during meiosis 1 or 2.
-Often occurs during meiosis 1 in female gametes
-it can occur in men but much later in life at about ~60 years old

47

What is polyploidy?

=more than 2 sets of homologous chromosomes
ex.
2 sperm--1 egg
1 sperm--diploid egg

48

Down syndrome... what is its MAIN cause?

47 chromosomes (21)
-retardation
-heart problems
-early onset alzheimers

main cause: maternal meiosis I

49

Kleinfelter syndrome

XXY
47

50

XYY syndrome

XYY 47
-very tall
-severe acne
lots in prison population?

51

Turner Syndrome

45 XO
-monosomy X
"webbed neck"
infertile
-could also have mosaic turners which are fertile therefore it is important to know where its full turners or not
-this is the SINGLE MOST COMMON ABNORMALITY IN ABORTIONS

52

Edward Syndrome

47
trisomy 18
-mental retardation
-overlap of middle and index fingers
-only 5% survive to 1 year

53

Patau Syndrome

47
trisomy 13
-microcephaly
polydactyl

54

Prader Willi

-paternal chromosome
-15 mutation
-fat
-short stature

55

Angelmans Syndrome

-From maternal side
-severe
-absence of speech

56

Whats the difference between genetics and genomics?

genetics: study of traits
genomics: is the study of genes

57

Inactivating changes in genes

-these are more common that activating changes
-mutations which reduce expression
-reduce activity of protein
-can alter splicing balance

58

What are reasons for gaps in the genome?

1. chromosomes are not continuous
2. some sequences are hard to read high GC
3. some sequence is hard to align--repeats

human genome is the ARTIFICIAL reconstruction of chromatin

59

What is some evidence for a genetic contribution to a disease?

1. congenital disorders
2. family hx
3. cross cultural
4. multigenerational
5. GWAS
6. identical twins separated at birth *ideal*
7. expression analysis

60

what is missing heritability?

-we know its heritable but we do not know the gene for it

61

Lamina A mutations

C--> T conversion
-mutation is absent in both parents
-usually acquired from a gremlin mutation
-it is what causes progeria

62

What is the difference between family Hx and Genetic status?

They are often used interchangeably but they are 2 different things

Family hx: stress, diet, exercise, infections, drugs/alcohol, exposure level to various things

genetic statusL shuffling, mutation to germ line, donor egg, adoption


where do they overlap? SNPs, most disease risks

63

What are PROBLEMS with family hx?

-time consuming
-not recorded in a usable format
-mistakes in recalling cause of death
-many know little about health hx due to secrecy, and low privacy rates
-adoption or donor eggs
-false paternity
-health records die with people

64

What are some advantages to multi-generational pedigree analysis?

-families have low genetic noise (they are very similar)
-example ashkenazi jews
mormons

65

gene--disease replationships

1. gene is perfectly associated with disease
*high penetrance- typical of monogenic

2. gene is poorly associated with disease
*low penetrance- typical of multi genic diseases

3. gene is strongly associated with disease but at variable levels
*high penetrant but variable EXPRESSIVITY

66

What are the steps to test pre-implantation embryos for IVF?

-induct the F to produce multiple oocytes
-harvest the embryos by transvaginal aspiration with US
-IVF with fathers sperm
-Harvest one of the 8 cells
-test cells for known mutations that you are looking for
-only implant the unaffected embryos