NANN genetics Flashcards
genetics
The science of human biologic
variation
mutation
A permanent, hereditary change
in the sequence of the DNA
DNA
A doublestranded nucleic acid built of nucleotides
containing a phosphate group, a nitrogenous base (adenine, thymine, guanine, or
cytosine), and the sugar deoxyribose
Chromosome
Structural unit composed of
DNA on a framework of protein. Chromosomes carry genetic information. Each human cell has
23 pairs of chromosomes.
Autosome
Nonsex chromosome; each
human cell has 22 pairs of autosomes
Sex chromosome
Chromosome that contains the genes determining sex; each human cell has two sex chromosomes (i.e.,
one pair). Based on their appearance, the
chromosomes of males are identified as
XY and those of females as XX
Karyotype
the chromosome constitution of an individual
gene
a sequence of chromosomal DNA that can specify the sequence of aminoacids in a particular polypeptide, inherited form parents
Allele
Alternate form of a gene found at the same locus (position) on homologous (the same or similar)
chromosomes. Alleles segregate during meiosis, and an individual receives only one of each pair of alleles from
each parent. Only two alleles can be present in any one individual
Homozygous
Having two identical alleles for a particular gene
heterozygous
Having two different alleles for a particular gene
genotype
An individual’s genetic constitution; the alleles present at one locus
Phenotype
The observed biochemical, physiological, and morphological characteristics of an individual (e.g.,
blue eyes, fair skin), as determined by his or her genotype and the environment in which it is expressed
Pedigree
A standard chart that simultaneously displays family relationships and phenotypes. A pedigree is constructed of shapes connected by lines.
cell division
mitosis (one division-used for growth, repair and asexual reproduction) and meiosis (two divisions- use for sexual reproduction)
nondisjunction
most frequent cause of all chromosome disorders; occurs when paired chromosomes fail to separate during cell division; example: before fertilization: trisomy or monosomy; after fertilization: mosaicism
trisomy
three copies of one chromosome are present in one cell
monosomy
one chromosome from a pair is missing
polyploidy
The presence of any multiple of the basic haploid chromosome number (n) other than the diploid number (2n; e.g., 3n [69 chromosomes], 4n [92 chromosomes])
chromosomal structure abnormalities
deletion, duplication, inversion, nonreciprocal translocation, reciprocal translocation
deletion
A missing sequence of DNA or a
missing part of a chromosome
duplication
An extra copy of a gene or DNA sequence, usually caused by misaligned pairing in meiosis
inversion
A part of a chromosome that has moved from its normal location; the normal sequence may be reversed
nonreciprocal translocation
A piece that has broken off of one chromosome and become attached to another chromosome
reciprocal translocation
Exchange of parts between two chromosomes. If the chromosome exchange does not break any genes,
then the person is healthy and is called a translocation carrier
Autosomal Abnormalities examples
Trisomy 21, 18, 13, Cri du chat
Sex chromosome abnormalities
monosomy X(Turner); XXX syndrome; XXY (Klinefelter syndrome); XYY syndrome
Trisomy 21/ Downs syndrome
most common, maternal age; nondisjunction: FEATURES: Hypotonia, flatted facial profile, poor moro, hyperflex joints, excess skin on the back of the neck, slanted palpebral fissures, dysplasia of pelvis, anomalous auricles, congenital heart defects, transverse palmar crease; GI anomalies: duodenal atresia; IQ 50; males always infertile, age span 49
Trisomy 18/ Edward syndrome
95% aborted; female to male 3:1’ advance maternal age; FEATUREs: severe mental deficiency, congenital heart defects, clenched hands overlapping fingers; severe hypotonia, prominent occiput, single umbilical artery, short sternum; survival average 14.5 days
cryptorchidism
undescended testis
ptosis
drooling eyelids
Trisomy 13/ Patau syndrome
FEATURES: severe mental deficiency; congenital heart defects; cleft lip and palete; holoprosencephaly, microcephaly, microphthalmia, deafness, polydyctaly, skin effects of posterior scalp; median survival age 7 days
holoprosencephaly
incomplete development of forebrain and olfactory and optic nerve; Trisomy 13
cri du chat syndrome
deletion on chromosome 5; severe mental retardation, a cat like cry, microcephaly, slow growth, hypotonia, hypertelorism; with support affected individuals attain at level pf 5-6 year old
hypertelorism
extreme width between the eyes
Turner syndrome / monosomy X
nondisjunction in paternal meiosis; FEATURES: ovarian dysgenesis with hypoplasia or absence of germinal elements; shield like chest; congenital lymphedema (puffiness); RX: growth hormone, estrogen replacement
XXX syndrome
errors of maternal meiosis; low IQ; above average in statue; sex development usually normal
XXY Klinefelter syndrome
Barr body; FEATURES: IQ 85-90; poor psychosocial development; tall and this statue; hypogonadism and hypogenitalism, infertility; RX: testosterone
XYY syndrome
YY sperm; not dysmorphic but large teeth, prominent glabella and long ears; increased risk for behavioral problems; normal fertility
Mendelian Single-gene Disorders
autosomal dominant, autosomal recessive, x-linked dominant, x-linked recessive
autosomal dominant disorder
only one copy of single abnormal gene is required; appears in every generation; 50% transmission chance;
autosomal recessive disorder
trait characteristic appears only in siblings; two copies of gene are required; 25% ; consanguinity
x-linked dominant disorders
affected males transmit the traits to all daughters not to sons; females are more likely to express the trait
x-liked recessive disorders
almost exclusively in males; trait never transmitted directly from father to son;
common mendelian single-gene diseases
Cystic Fibrosis, Congenital myotonic dystrophy, osteogenesis imperfecta, infantile polycystic kidney disease; vitamin D-resistant rickets
Cystic Fibrosis defect
autosomal recessive; protein abnormality that is responsible for chloride transport that leads to thick mucous in lumens of pancreas, lungs, intestines, biliary tract, and appendix
CF clinical features
meconium ileus, intestinal atresia, prolonged jaundice
CF diagnosis and tests and RX
sweat test; RX: abx, bronchodilators, steroids, enzymes, fat soluble vitamins
Congenital myotonic dystrophy defect
autosomal dominant; TYPE I: DMPK triplet repeat of cytosine-thymine-guanine; abnormal CNS
congenital myotonic dystrophy clinical features
poor sucking, generalized hypotonia, facial diplegia, clubfoot, mental retardation
congenital myotonic dystrophy DX and RX
muscle biopsy, serum creatinine kinase, electromyography; nerve conduction velocities are normal; no RX; failure to thrive (in infancy)
osteogenesis imperfecta defect
autosomal dominant; I-VI types
Osteogenesis imperfecta TYPES and features
I: postnatal bone fragility, blue sclerae; easy bruising
II: minimal calvarial mineralization, beaded ribs, compresses femurs
III: prenatal bone fractures, short stature, deafness
IV: normal to moderately short stature with significant bone deformity; normal sclerae,
V: moderate to severe tendency to fracture vertebrae and long bones, ligamentous laxity
VI: mild to moderate expression; postnatal onset at 4-18months;
infantile polycystic kidney disease defect
autosomal recessive dx on prenatal US
infantile polycystic kidney disease clinical features
potter facies: low-set ears, short nose, deep eye creases, micrognathia; clubfoot, large palpable bilateral renal masses; HPT; cardiac hypertrophy and CHF
vitamin D- resistant rickets defect
x-linked dominant; features: growth retardation, childhood rickets, reduced serum phosphate
vit D-resistant rickets RX
large dose of vit D and oral phosphate
mosaicism
the condition in which there are two or more cell lines derived froma single zygote that are different genetically because of the postzygotic mutation or nondisjunction
anticipation
the progressively earlier appearance and increased severity of a disease in successive generations
imprinting
the differential expression of genetic material, at either a chromosomal or an allelic level, depending on whether the genetic material is inherited from male or female parent
mitochondrial DNA
the DNA in the circular chromosome of the mitochondria, which is inherited from the mother
multifactorial disorders examples
no distinctive pattern of inheritance: congenital heart defects; Cleft lip; Pyloric stenosis; Neural tube defect; clubfoot(talipes equinovarus); Hirschprung disease; Hypospadias
Congenital Heart Defects
identified on prenatal US; heart murmur, cardiac failure, cyanosis; infant might sweat and become breathless at feedings
cleft lip
feeding difficulties; surgery in several stages
pyloric stenosis
severe feeding problems with nonbilious projectile vomiting; “olive” firm, non-tender and mobile hard pylorus; DX at 3-12 weeks; surgical correction
Neural Tube Defects NTD
malformation of developing brain and spinal cord
anencephaly
absence of forebrain and skull vault
rachischisis
fatal condition in which NTD extends the length of the spine
encephalocele
herniation of the meninges and brain through the skull
spina bifida cystica
myelomeningocele and meningocele
myelomeningocele
most common type of NTD; a cyst or sac containing portion of the spinal cord and meninges protrudes through an opening in the vertebrae
meningocele
type of spina bifida cystica: sac containing only the meninges, the spinal cord is in proper position
spina bifida occulta
the NTD is covered by a tuft of hair or layer of skin; one or two vertebrae are not properly fused; spinal cord and meninges are normal
NTD DX
prenatal: increased maternal serum alpha-fetoprotein levels; increased acetylcholinesterase; high-resolution US
NTD prevention
prenatal folic acid
NTD nursing interventions
prevent infection: cover sac, keep infant prone, sterile plastic over anus; observe for hydrocephalus
hydrocephalus S&S
rapid increase in head circumference; bulging fontanelles; shiny scalp; irritability
clubfoot/talipes equinovarus clinical features
male to female 2:1; the affected foot is held in flexed (equinus) and inturned (varus) position
Hirschsprung disease defect
failure to complete cranial to caudal migration of neural crest cells at 8-10 weeks gestation; absence of submucosal and myenteric ganglion cells
Hirschsprung disease clinical features
DX in the first 2 years; neonate fail to pass mec in first 48 hours of life; lack of peristalsis result in chronic constipation; emesis bile stained with texture and smell of feces; bowel removal and temporary colostomy
Hypospadias clinical features
the urethral orfice is situated on the ventral aspect of the penis at a site proximal to the normal opening; urethra shorter; need to delay circumcision
teratogens
agents that produce or increase the incidence of congenital malformations
teratogens examples
DRUGS: alcohol, smoking, ACE and ARBs; chemo agents, cocaine, warfarin, Accutane, phenytoin, streptomycin(hearing loss), tetracycline (dental staining), thalidomide, trimethadione, valproic acid …INFECTIONS: CMV, Rubella, HIV, Toxoplasmosis, Herpes simples, varicella-zoster; MATERNAL DISORDERS: insulin-dependent DM,
FAS clinical features
microcephaly, short palpebral fissures, epicenthic folds, ptosis, small midface
Newborn Screening diseases
PKU, Congenial hypothyroidism, galactosemia, congenital adrenal hyperplasia, biotinidase deficiency, sickle cell disease, maple syrup urine diseasel AUTOSOMAL RECESSIVE; most cause mental retardation
prenatal testing
US, Nuchal scan, chorionic villus sampling, amniocentesis, maternal serum AFP, preimplantation genetic testing, percutaneous umbilical blood sampling;
ULTRASONOGRAPHY
5 weeks; organ system and anatomical scan 16-20 weeks; no maternal or fetus risk
NUCHAL SCAN
11-13 weeks; assesses the amount of fluid behind the neck of the fetus: nuchal translucency; no maternal or fetus risk
Chorionic villus sampling
10-12 weeks; transcervical sampling of placental tissue; ; karyotype; detection of chromosomal abnormalities; maternal risk: vaginal bleeding, infection, acute AF leakage; fetal risk: miscarriage; might stop development of feet and hands if done too early
Amniocentesis
14-18 weeks; insertion of a spinal needle into the uterus through the abdomen to aspirate 20-30 ml of AF; detection of chromosomal abnormalities; maternal risk: vaginal bleeding, AF leakage, infection; fetal risk: fetal loss, needle puncture, Rh sensitization, premature labor
Maternal serum AFP
16-20 weeks; detect NTD and chromosomal abnormalities; mother blood test; no risk
Human Genome Project
1990 launched; 2006 published
mitosis
one division
two daughter cells per cycle
daughter cells are genetically identical to each other and to the parent cell
the # of chromosomes in the daughter cells is the same as the # in the parent cell
occurs in somatic cells
occurs through the life circle
growth, repair, asexual
meiosis
two divisions
four daughter cells per circle
daughter cells are genetically different from each other and from the parent cell
the # of chromosomes in the daughter cell is half that of the parent cell
after sexual maturity
sexual reproduction
transverse palmar crease
simian crease
brushfield spots
white speckling of the iris
dermatolyphics
ridged pattern of kin on fingers
micrognathia
small jaw
coloboma
cleft of the iris that looks like a key
