genetics Flashcards Preview

clin med > genetics > Flashcards

Flashcards in genetics Deck (83):
1

types of prenatal genetic analysis

Karyotype, FISH, microarray, genome sequencing

2

how many generations should be tested in the genetic work-up?

2-3 generations

3

what should be used in the standard pedigree info?

initials/names of family
ages or DOB
ages and cause of death
details of a disorder
min of 2-5 generations
ethnic background including religious group

4

who are at-risk family members?

consanguinity
ashkenazi jews
african, mediterranean
BRCA
caucasians

5

what is termed as the physical location of a gene?

locus

6

what is the version of a gene? letter used to represent a gene

allele

7

what is considered a "normal" allele?

wild-type

8

what is considered an abnormal version of the gene associated with a trait/disorder?

mutant

9

structures which house the gene

chromosome

10

how many chromosomes do we have?

46 (23 pairs)

11

what is the "central dogma"

process of replication, transcription and translation

12

what is the message(nucleotides) encoded in RNA called? 3 letter words

codon

13

what are the first 22 pairs of chromosomes called?

autosomes

14

What are a combination of alleles at adjacent locations on a chromosome that are inherited together. Or a set of single-nucleotide polymorphisms

haplotype

15

Production of RNA using DNA code as template

transcription

16

Production of a protein using RNA code as template

Translation

17

Actively forming the string of proteins in to a 3D form that can be used by the body

folding

18

sites at which a single letter in the DNA code has been swapped for a single alternate letter

single nucleotide polymorphisms (SNPs)

19

Produces a new cell with the same number of chromosomes as the original

mitosis

20

Occurs in Germ cells, Two phases

meiosis

21

Occurs with autosomes (somatic)

mitosis

22

most compact phase of mitosis?

metaphase

23

two nuclear membranes form in which stage of mitosis?

telophase

24

The centromere splits, start to draw to opposite ends during which stage of mitosis?

anaphase

25

This is when different mutations occur on the same gene

allelic heterogeneity

26

This occurs when different genes cause the same disease (e.g. hearing loss)

Locus/non-allelic heterogeneity

27

This occurs when different phenotypes occur with mutations on the same gene (e.g. RET gene lic heterogeneity associated with Hirschprungs and Multiple Endocrine Neoplasia)

Phenotypic heterogenity

28

what is penetrance?

when you inherit the gene, but are "normal" - incomplete penetrance (Ex BRCA)

29

what is expressivity?

seen in all that have the gene, but expressed differently (variable expressivity, such as Marfan's)

30

Increased severity in subsequent generations
CNS disorders
Trinucleotide repeat expansion
HD, Myotonic dystrophy

anticipation

31

what is x-linked?

no male to male, all daughters of males are carriers

32

what is co-dominance?

both alleles of the gene pair contribute to the phenotype (blood groups)

33

what are examples of non-mendelian inheritance?

genomic imprinting
mosaicism
mitochondrial DNA mutations

34

autosomal dominant disorders

huntington disease
myotonic dystrophy
Neurofibromatosis,Tuberous Sclerosis
Urinary Polycystic Kidney Disease, Familial Adenomatous Polyposis, Marfan’s syndrome
Ehlers-Danlos syndrome

35

Autosomal Recessive Disorders

Cystic Fibrosis
Sickle Cell Anemia
Tay-Sachs Disease
Phenylketonuria (PKU)
Galactosemia
Homocystinuria
Lysosomal storage disease
Fredereich ataxia
Spinal muscular atrophy

36

X-Linked Disorders

Male-hemizygous (Y not homologous to X)
Heterozygous female can manifest some symptoms (less than male)
Example: G6PD deficiency

37

example of y-linked disorder

sertoli-only cell syndrome (complete absence of germ cells in testis)

38

what are mitochondrial disorders?

maternal inheritance, leber hereditary optic neuropathy

39

what is mosaicism?

Mitotic errors develop early and result in two or more populations of cells with different chromosomal information in the same person.
Common in X, Y

Occurs post-zygotically

40

This chromosome occurs when two broken ends of the same chromosome fuse

ring

41

This is when a chromosome breaks and the fragment re-attaches to the original chromosome in a reverse orientation

inversion

42

This is when a chromosome lacks certain genes or there is an absence of a segment of DNA.

deletion

43

I am a point mutation that exhanges a nucelotide for another one= changes in amino acids. may affect protein function

missence

44

sickle cell disease is an example of what type of mutation?

missence

45

I am a point mutation changing a codon for an amino acid into a STOP codon.Usually non-functional

nonsense

46

autosomal dominant disorder characterized by the development of bilateral vestibular schwannomas. average age of onset is 18-24 years

NF2 (bilateral acoustic neurofibromatosis, or central NF)

47

autosomal dominant disorder which manifests in the 3rd or 4th decade and leads to complaints of muscle stiffness and is evidenced by the marked delay that occurs before affected muscles can relax after a contraction

myotonic dystrophy

48

what is the most life threatening inherited disease worldwide? characterized by numerous fluid-filled cysts that result in massive enlargement of the kidneys

polycystic kidney disease

49

difference between Autosomal Recessive Polycystic Kidney disease and autosomal dominant

autosomal recessive is a disease of childhood and linked to hetogenous mutations in a single gene.
autosomal dominant mostly seen in adults which leads to uncontrolled/regulated cell growth

50

Gene that provides instructions for making a protein called fibrocystin (sometimes known as polyductin) which is present in adult and fetal kidney cells.

PKHD I

51

what is the function of PKHD I that we are concerned with in PKD?

cell proliferation

52

autosomal dominant disorder where the person will have hundreds to thousands of adenomatous polyps in the colon and has a nearly 100% risk of developing CA by middle age if colon is not surgically removed

Familiar Adenomatous polyposis (FAP)

53

what do FAP patients present with?

numerous colorectal ademonas by the second or third decade of life

54

autosomal dominant disorder which causes defects in in collagen and other proteins of various tissues. patients will have skin elasticity, joint hypermobility, tissue fragility, multiple ecchymoses, and subcutaneous pseudotumors

Ehlers-Danlos Syndrome

55

autosomal dominant connective-tissue disorder. cardinal features: tall stature, ectopia lentis, mitral valve prolapse, aortic root dilation, and aortic dissection

marfan syndrome

56

what percentage of marfan's patients have an affected parent?

3/4

57

is marfan syndrome fully penetrant?

yes

58

marfan syndrome results from mutations in which gene?

fibrillin I gene which encodes for the glycoprotein fibrillin - a major building block of microfibrils, which constitute the structural components of the suspensory ligament of the lens

59

abnormalities involving microfibrils in marfan's weaken what?

the aortic wall, which leads to progressive aortic dilation and eventual aortic dissection

60

4 major diagnostic findings for marfan syndrome

dilation or dissection of the aorta@ level of the sinuses of valsalva

ectopia lentis

dural ectasia

4 or 8 specific skeletal features

61

autosomal dominant. this is the "receptor disease" caused by a mutation of the gene encoding the receptor fo rLDL, which is involved in the transport and metabolism of cholesterol

familial hypercholesterolemia - as a consequence of the receptor abnormalities there is a loss of feedback control and the patient will develop elevated cholesterol levels. 1 in 500 individuals

-heterozygotes with one mutant gene: 2-3 fold elevation in plasma cholesterol

-Homozygotes: most severely affected, 5-6 fold increase in plasma cholesterol levels

62

co-dominant disorder where there is a deficiency of the protease inhibitor alpha I-antitypsin which results in a predisposition to pulmonary emphysema and hepatic cirrhosis. accounts for approximately 2% of COPD cases in america

alpha I antitrypsin Deficiency

63

autosomal recessive disorder caused by a defect in the PAH gene which codes for pheylalanine hydroxylase, an enzyme that converts phenylalanine to tyrosine in the liver. part of newborn screen, with strict adherence to diet can avoid most of the symptoms.

PKU

64

clinical signs/symptoms of PKU

fair skin, blonde hair, blue eyes.
mental retardation, hyperactivity, seizures and eczema characterize untreated patients. hallmark sign "mousy" odor of hair, skin and specifically urine

65

treatment of PKU

restrict dietary pheylalanine and supplement tyrosine

66

autosomal recessive disorder caused by almost total I-phosphate uridyl transferase deficiency. accumulation of galactose I-phosphate which results in injury to parenchymal cells of the kidney, liver and brain

galactosemia

Tx is a galactose free diet

67

autosomal recessive disorder involving a gene that is involved in copper transport. leads to increased copper storage and ultimately liver disease

wilson's disease

68

when does wilson's disease first appear?what is the initial feature?

between ages of 6 and 40. liver disease (jaundice, fatigue, loss of appetite and abdominal swelling)

69

autosomal recessive disease causing hexosaminidase A deficiency. Ashkenazi jews. relentless deterioration of mental and physical abilities which commences at six months of age and usually results in death by the age of four

Tay Sachs

*no treatment for these patients

70

most common cause of inherited MR

fragile X syndrome

71

clinical features of fragile X

large protruding ears
large testes
elongated face
stereotypic movements (hand flapping)
CGG trinucleotide repeated

72

chromosomal abnormality involing absence of all or part of one X chromosome (X monosomy). most common sex chromosome abnormality of human females. (45, XO karyotype)

turner syndrome

73

keys to diagnosis of turner syndrome

short stature with normal GH levels

hypogonadism
primary amenorrhea or early ovarian failure

epicanthal folds, webbed neck, short fourth metacarpals

renal and cardiovascular anomalies

74

syndrome characterized by severe hypotonia and feeding difficulties in early infancy followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity

prader willi syndrome

75

down's syndrome, major cause of mental retardation. chromosome count is 47

trisomy 21

76

characteristics of trisomy 21

Flat facial profile
Oblique palpebral fissures
Epicanthic folds

Predisposed to Leukemia, Congenital Heart disease and early Alzhiemers

77

edwards syndrome, associated with severe intellectual disability, many infants die within their first month

Low birth weight
Small, abnormally shaped head
small jaw and mouth
Clenched fists with overlapping fingers; heart defects
Abnormalities of other organs.

trisomy 18

78

patau syndrome. nearly 50% die within the first month, relatively few survive past 3 years of age
Holoprosencephaly
Eye anomalies (microphthalmia, anophthalmia, or coloboma)
Cleft lip and palate
Polydactyly
Cardiac defects
Low birth weight

trisomy 13

79

characterized by an extra copy of the Y chromosome in each of a man's cells. may be taller than average

XYY - most males with this have normal sexual development and are able to father children

Associated with an increased risk of learning disabilities and delayed development of speech and language skills.
Delayed development of motor skills (such as sitting and walking), hypotonia, motor tics, and behavioral and emotional difficulties are also possible.
These characteristics vary widely among affected boys and men

80

trisomy X, characterized by the presence of an additional X chromosome in each of a female's cells. may be taller than average

XXX

81

one of the most frequent forms of genetic disease involving the sex chromosomes as well as one of the most common causes of hypogonadism in males.

Klinefelter syndrome - rarely diagnosed before puberty

82

this is a component of the 22QII deletion syndrome

DiGeorge syndrome - fairly common (1 in 4,000), often missed because of variable clinical features

83

clinical features of DiGeorge Syndrome

congenital heart defects
abnormalities of the palate
facial dysmorphism
developmental delay
Variable degrees of T-cell immunodeficiency
Hypocalcemia