Human Genetics Exam 2

define dysmorphology

the study of human congenital malformations and birth defects

dysmorphology combines knowledge of:

• genetic principles

• developmental mechanisms

• natural history of congenital abnormalities

what are common dysmorphologies related to Down Syndrome?

• upslanting palpebral fissures

• flattened nasal bridge

• brushfield spots

• low-set, small, folded ears

• short neck

• epicanthal folds

what is the dysmorphology term for a child’s head being either to large or small

microcephaly and macrocephaly

define hypertelorism

eyes are too far apart

define hypotelorism

eyes are too close together

define telecanthus

the inner corners of the eye are displaced laterally

define epicanthal folds

folds of skin overlapping the inner canthi

define blepharophimosis

small eye openings

define prognathia

jaw protrudes out

define retrogneathia

jaw retracts

define micrognathia

small jaw

define polydactyly

extra digits

define syndactyly

fused digits, deficiencies, abnormal creases

define brachydactyly

short digits

define arachnodactyly

long digits

define oligodactyly

missing digits

what enzyme converts testosterone to dihydrotestosterone

5a-reductase

what type of inheritance does Guevedoces display

autosomal recessive

Guevedoces is primarily what type of mutation?

missense

Pseudoautosomal regions (PAR1 and PAR2) make up __-__% of the chromosome

5-10%

What is the other 95% (not PAR1 and PAR2) of the male chromosome referred to as

Male Specific Region

what does the SRY gene code for

transcription factor protein - stimulates male development and sends signals to gonads to degenerate female structures

define pronucleus

the sperm/egg nucleus after sperm has entered the ovum at fertilization but before fusion of the pronuclei

what are sex-limited traits

traits that affect a structure or function occuring only in one sex - may be autosomal or X-linked

examples of sex limited traits

• beard growth

• milk production

• preeclampsia in pregnancy

what are sex-influenced traits

allele is dominant in one sex but recessive in the other - difference in expression can be caused by hormonal differences between sexes

sex-influenced trait examples

pattern baldness in humans - heterozygous male is bald, heterozygous female is not

what is the paternal age effect?

increased risk of health disorders in children with older fathers

examples of disorders that display the paternal age effect:

• achondroplasia

• crouzan syndrome

• multiple endocrine neoplasia 2

• pfeiffer syndrome

• thanatophoric dysplasia

how many possible combinations of maternal chromosomes via independent assortment

2²³ = ~8,000,000

What is the MHC

Major Histocompatibility Complex - codes for proteins to help the immune system identify foreign antigens

what is another name for the MHC

HLA region - Human Leukocyte Antigen

where is the MHC located

Located on the short arm of chromosome 6

functions of the MHC

• presentation of intracellular and extracellular pathogens

• inflammation

• neural development

• potentially related to mate selection

• environmental factor responses

What are the three regions of MHC called

Class I, Class II, Class III

Describe Class I region of MHC

• expressed on nearly all nucleated cells

• presenting endogenous (intracellular) peptides to CD8+ T cells

• genes: HLA-A, HLA-B, HLA-C, etc

CD8 cell function

directly kill infected immune cells

describe class II region genes of MHC

• expressed on antigen presenting cells (APCs)

• presenting exogenous (extracellular) peptides to CD4+ T cells

  • adaptive immunity

• genes: HLA-DP, HLA-DQ (two letters = class 2)

describe class III region genes of MHC

• expression affects inflammation and immunity

  • complement proteins and cytokines

• supports both innate and adaptive immunity

• genes: Complement component 4 (C4), TNF-a/b, etc

____ genes are the most polymorphic genes in the human genome

MHC

what does high allelic diversity allow for

better immune recognition but complicates transplantation compatibility

what is the most polymorphic gene in the human genome

HLA-B

True/false: certain MHC alleles may confer resistance or susceptibility to autoimmune responses

true

which type of selection maintains MHC diversity and why?

balancing selection - prevents any single allele from becoming fixed or lost in a population

_____ genotypes can present a wider variety of pathogen-derived antigens

heterozygous - harder for antigens to escape immune detection

does infectious disease promote or inhibit HLA diversity

promote

what is a haplotype

a set of genes or genetic markers that are inherited together from one parent

siblings have a ___% chance of a full HLA match

25%

mismatched HLA alleles can lead to ____________ or organ rejection

graft-versus-host-disease - transplanted immune cells (graft) attack the recipient’s (host) healthy tissues

what is linkage disequilibrium

the nonrandom association of alleles at different loci in a population

define cytogenetics

the study of chromosomes and their abnormalities

Benefits of using Fluorescent in situ hybridization

• sequence and chromosome specific places in DNA

• simultaneous assessment of multiple genetic targets in an intact cell

• relatively easy interpretation

• easy to perform

• short time-to-result

• quantitates genetic changes cell-by-cell

abnormal chromosomes account for at least __% of spontaneous abortions

50%

nondisjunction during meiosis I results in

both homologs in one gamete

nondisjunction during Meiosis II results in

both sister chromatids in one gamete

frequently seen trisomies:

21, 18, 13

Describe Trisomy 18

• Edward’s Syndrome

• commonly do not survive

• mental and physical disabilities

• oddly clenched fists

Describe Trisomy 13

• Patau Syndrome

• very rare and generally do not survive past 6 months

• serious mental and physical disabilites

• eye fusion

name ways you can diagnose aneuploidies

• standard cytogenic

• QF-PCR (quantitative fluorescenting)

• NIPT (noninvasive prenatal testing)

• serum and ultrasound screening

Describe Klinefelter syndrome

• 85% nondisjunction

• XXY

• common cause of male infertility

• incomplete sexual development, rudimentary testes and prostate, long limbs, large hands and feet, breast tissue development

Describe Jacob’s Syndrome

• XYY aneuploidy

• 96% are phenotypically normal

• modest phenotypes - great height, acne, speech and reading disabilities

describe XXYY syndrome

• arises due to unusual oocyte and sperm

• more severe behavioral problems than Klinefelter’s - OCD, learning disabilities

• infertile and treated with testosterone

Describe Turner Syndrome

• XO

• 99% of fetuses die in utero

• features: short stature, webbing at the back of neck, incomplete sexual development, impaired hearing

• individuals who are mosaics may have children

Triplo-X Syndrome

• few modest effects on phenotype

• tallness, menstrual irregularities, and slight impact on intelligence

• X inactivation of two X chromosomes occurs

Reciprocal Translations

• two non-homologous chromosomes exchange parts

• usually healthy because they have the normal amount of genetic material

Robertsonian Translocation

• two nonhomologous, acrocentric chromosomes break at the centromere and the long arms fuse

is nondisjuction more common in males or females

females

what do mitochondrial genomes code for

polypeptides required for mitochondrial respiratory chain

what type of diseases result from mitochondrial mutations

• monogenic disorders that affect the nervous system, muscles, heart, and endocrine organs

• mutations with milder contribution to common complex traits and late-onset disorders

does mtDNA contain introns?

no

is there recombination in mtDNA

no

what makes mtDNA easily mutable

high exposure to free radicals

how many copies of DNA do each mitochondrion contain

2-10

functions of the mitochondria

• cellular metabolism

• intracellular calcium signalling

• biogenesis of iron-sulfur clusters

• apoptotic cell death

define heteroplasmy

mosaicism for mitochondrial DNA variants, usually within a single cell

levels of heteroplasmy can vary:

• between cells in the same tissue or organ

• from organ to organ in the same person

• between individuals in the same family

what is leber optical atrophy and what can it be the result of

impaired vision - mitochondrial disorders

describe Leber Hereditary Optic Neuropathy (LHON)

painless, progressive loss of central vision - degeneration of retinal ganglion cells and their axons, leading to acute loss of central vision

missense mutations - low penetrance with males more likely to become blind

Describe myoclonic epilepsy with ragged red fibers (MERRF)

• tRNA mutation

• progressive epilepsy and dementia, onset late childhood-adulthood

are mtDNA point mutations or mtDNA deletions inherited

point mutations

are mtDNA point mutations or mtDNA deletions homoplasmic

point mutations

describe Friedreich’s Ataxia

• triplet/trinucleotide repeat disorder

• results in cell death, in particular of neurons, heart muscle, and beta cells in pancreas

5 hardy weinburg assumptions

• infinite number of individuals in the population

• random mating

• no new mutations

• no migration

• no natural selection

what is genetic load

collection of recessive deleterious alleles in a population

describe population bottlenecks

occurs when a large population is drastically reduced in size - Ashkenazi Jews

Founder Effect

all individuals in a population with a certain illlness have the same mutation - BRCA1 breast cancer among Ashkenazi Jewish people

describe balanced polymorphism

harmful recessive alleles are replaced by new mutation, and persistence in heterozygotes - sickle cell